Updated on 2021/06/11

写真a

 
OGI Tomoo
 
Organization
Nagoya University Research Institute of Environmental Medicine Division of Stress Adaptation and Protection Professor
Title
Professor

Degree 1

  1. 博士(理学) ( 2001.3   京都大学 ) 

Research Interests 14

  1. DNA repair; human genetics; nucleotide excision repair; genome

  2. 転写と共役したヌクレオチド除去修復

  3. 突然変異

  4. 発がん

  5. 放射線DNA損傷

  6. Human Genetics

  7. 乳癌

  8. ヌクレオチド除去修復

  9. タンパク質間相互作用

  10. ゲノム医科学

  11. DNA損傷修復

  12. DNA repair; human genetics; nucleotide excision repair; genome

  13. DNA修復

  14. BRCA2

Research Areas 6

  1. Life Science / Dermatology

  2. Life Science / Pathological biochemistry

  3. Environmental Science/Agriculture Science / Radiation influence

  4. Life Science / Medical biochemistry

  5. Environmental Science/Agriculture Science / Chemical substance influence on environment

  6. Life Science / Molecular biology

▼display all

Research History 2

  1. Nagoya University   Research Institute of Environmental Medicine Division of Stress Adaptation and Protection   Professor

    2015.4

  2. Nagoya University   Research Institute of Environmental Medicine (RIeM)   Professor

    2015.4

 

Papers 93

  1. Predominant cellular mitochondrial dysfunction in the TOP3A gene-caused Bloom syndrome-like disorder

    Jiang Wenjun, Jia Nan, Guo Chaowan, Wen Juan, Wu Lingqian, Ogi Tomoo, Zhang Huiwen

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE   Vol. 1867 ( 6 ) page: 166106   2021.6

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    Publishing type:Research paper (scientific journal)   Publisher:Biochimica et Biophysica Acta - Molecular Basis of Disease  

    DOI: 10.1016/j.bbadis.2021.166106

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  2. Hereditary mucoepithelial dysplasia/autosomal-dominant IFAP syndrome is a clinical spectrum due to SREBF1 variants.

    Murase C, Takeichi T, Nomura T, Ogi T, Akiyama M

    The Journal of investigative dermatology   Vol. 141 ( 6 ) page: 1596 - 1598   2021.6

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    DOI: 10.1016/j.jid.2020.09.035

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  3. Paradoxical Reaction in a Patient with Hidradenitis Suppurativa Undergoing Adalimumab Treatment.

    Ikeya S, Takeichi T, Taki T, Muro Y, Ogi T, Akiyama M

    Acta dermato-venereologica     2021.5

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    DOI: 10.2340/00015555-3844

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  4. The sodium-glucose cotransporter-2 inhibitor Tofogliflozin prevents the progression of nonalcoholic steatohepatitis-associated liver tumors in a novel murine model.

    Yoshioka N, Tanaka M, Ochi K, Watanabe A, Ono K, Sawada M, Ogi T, Itoh M, Ito A, Shiraki Y, Enomoto A, Ishigami M, Fujishiro M, Ogawa Y, Suganami T

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie   Vol. 140   page: 111738   2021.5

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    DOI: 10.1016/j.biopha.2021.111738

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  5. Cutaneous malignant melanoma in an elderly patient with intermediate junctional epidermolysis bullosa

    Yamashita Yuta, Taki Tomoki, Takeichi Takuya, Okumura Mao, Mori Shoichiro, Ito Yasutoshi, Ogi Tomoo, Yamada Motohito, Akiyama Masashi

    JOURNAL OF DERMATOLOGY     2021.5

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    Publishing type:Research paper (scientific journal)   Publisher:Journal of Dermatology  

    DOI: 10.1111/1346-8138.15951

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  6. MEDNIK-like syndrome due to compound heterozygous mutations in AP1B1

    Ito Y., Takeichi T., Igari S., Mori T., Ono A., Suyama K., Takeuchi S., Muro Y., Ogi T., Hosoya M., Yamamoto T., Akiyama M.

    JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY   Vol. 35 ( 5 ) page: E345 - E347   2021.5

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    Publishing type:Research paper (scientific journal)   Publisher:Journal of the European Academy of Dermatology and Venereology  

    DOI: 10.1111/jdv.17098

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  7. Transcription-Coupled DNA Repair: From Mechanism to Human Disorder

    van den Heuvel Diana, van der Weegen Yana, Boer Daphne E. C., Ogi Tomoo, Luijsterburg Martijn S.

    TRENDS IN CELL BIOLOGY   Vol. 31 ( 5 ) page: 359 - 371   2021.5

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    Publishing type:Research paper (scientific journal)   Publisher:Trends in Cell Biology  

    DOI: 10.1016/j.tcb.2021.02.007

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  8. Protein instability associated with AARS1 and MARS1 mutations causes Trichothiodystrophy.

    Botta E, Theil AF, Raams A, Caligiuri G, Giachetti S, Bione S, Accadia M, Lombardi A, Smith DEC, Mendes MI, Swagemakers SMA, van der Spek PJ, Salomons GS, Hoeijmakers JHJ, Yesodharan D, Nampoothiri S, Ogi T, Lehmann AR, Orioli D, Vermeulen W

    Human molecular genetics     2021.4

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    DOI: 10.1093/hmg/ddab123

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  9. [A case of Charcot-Marie-Tooth disease type 2Z caused by MORC2 S87L mutation mimicking spinal muscular atrophy].

    Yamamoto D, Oda R, Hisahara S, Ishikawa A, Ogi T, Shimohama S

    Rinsho shinkeigaku = Clinical neurology   Vol. 61 ( 4 ) page: 262 - 264   2021.4

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    Publishing type:Research paper (scientific journal)   Publisher:Clinical Neurology  

    DOI: 10.5692/clinicalneurol.cn-001542

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  10. Extensive multiple organ involvement in VEXAS syndrome.

    Takahashi N, Takeichi T, Nishida T, Takahashi Y, Sato J, Yamamura M, Ogi T, Akiyama M

    Arthritis & rheumatology (Hoboken, N.J.)     2021.4

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    DOI: 10.1002/art.41775

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  11. Temporal dynamics of the plasma microbiome in recipients at early post-liver transplantation: a retrospective study

    Okumura Toshihiko, Horiba Kazuhiro, Kamei Hideya, Takeuchi Suguru, Suzuki Takako, Torii Yuka, Kawada Jun-ichi, Takahashi Yoshiyuki, Ogura Yasuhiro, Ogi Tomoo, Ito Yoshinori

    BMC MICROBIOLOGY   Vol. 21 ( 1 ) page: 104   2021.4

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    Publishing type:Research paper (scientific journal)   Publisher:BMC Microbiology  

    DOI: 10.1186/s12866-021-02154-w

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  12. Identification of a novel causative mutation in KRT1 in diffuse palmoplantar keratoderma, facilitated by whole-exome sequencing.

    Takeuchi S, Takeichi T, Ito Y, Tanahashi K, Muro Y, Ogi T, Akiyama M

    European journal of dermatology : EJD   Vol. 31 ( 2 ) page: 264 - 265   2021.4

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    DOI: 10.1684/ejd.2021.4017

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  13. The wide-ranging clinical and genetic features in Japanese families with valosin-containing protein proteinopathy

    Ando Takashi, Nakamura Ryoichi, Kuru Satoshi, Yokoi Daichi, Atsuta Naoki, Koike Haruki, Suzuki Masashi, Hara Kazuhiro, Iguchi Yohei, Harada Yumiko, Yoshida Yusuke, Hattori Makoto, Murakami Ayuka, Noda Seiya, Kimura Seigo, Sone Jun, Nakamura Tomohiko, Goto Yoji, Mano Kazuo, Okada Hisashi, Okuda Satoshi, Nishino Ichizo, Ogi Tomoo, Sobue Gen, Katsuno Masahisa

    NEUROBIOLOGY OF AGING   Vol. 100   page: 120.e1 - 120.e6   2021.4

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    Publishing type:Research paper (scientific journal)   Publisher:Neurobiology of Aging  

    DOI: 10.1016/j.neurobiolaging.2020.10.028

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  14. Successful dupilumab treatment for ichthyotic and atopic features of Netherton syndrome.

    Murase C, Takeichi T, Taki T, Yoshikawa T, Suzuki A, Ogi T, Suga Y, Akiyama M

    Journal of dermatological science     2021.3

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    Publishing type:Research paper (scientific journal)   Publisher:Journal of Dermatological Science  

    DOI: 10.1016/j.jdermsci.2021.03.003

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  15. Two Cases of Porokeratosis with MVD Mutations, in Association with Bullous Pemphigoid

    Arisawa Yuki, Ito Yasutoshi, Tanahashi Kana, Muro Yoshinao, Ogi Tomoo, Takeichi Takuya, Akiyama Masashi

    ACTA DERMATO-VENEREOLOGICA   Vol. 101 ( 3 ) page: adv00423   2021.3

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    Publishing type:Research paper (scientific journal)   Publisher:Acta Dermato-Venereologica  

    DOI: 10.2340/00015555-3764

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  16. Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer's disease

    Sobue Akira, Komine Okiru, Hara Yuichiro, Endo Fumito, Mizoguchi Hiroyuki, Watanabe Seiji, Murayama Shigeo, Saito Takashi, Saido Takaomi C., Sahara Naruhiko, Higuchi Makoto, Ogi Tomoo, Yamanaka Koji

    ACTA NEUROPATHOLOGICA COMMUNICATIONS   Vol. 9 ( 1 ) page: 1   2021.1

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    Publishing type:Research paper (scientific journal)   Publisher:Acta Neuropathologica Communications  

    DOI: 10.1186/s40478-020-01099-x

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  17. Expanding the phenotype of biallelic loss-of-function variants in theNSUN2gene: Description of four individuals with juvenile cataract, chronic nephritis, or brain anomaly as novel complications

    Kato Kohji, Mizuno Seiji, Morton Jenny, Toyama Miho, Hara Yuichiro, Wasmer Evangeline, Lehmann Alan, Ogi Tomoo

    AMERICAN JOURNAL OF MEDICAL GENETICS PART A   Vol. 185 ( 1 ) page: 282 - 285   2021.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/ajmg.a.61927

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  18. Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome

    Oka Yasuyoshi, Hamada Motoharu, Nakazawa Yuka, Muramatsu Hideki, Okuno Yusuke, Higasa Koichiro, Shimada Mayuko, Takeshima Honoka, Hanada Katsuhiro, Hirano Taichi, Kawakita Toshiro, Sakaguchi Hirotoshi, Ichimura Takuya, Ozono Shuichi, Yuge Kotaro, Watanabe Yoriko, Kotani Yuko, Yamane Mutsumi, Kasugai Yumiko, Tanaka Miyako, Suganami Takayoshi, Nakada Shinichiro, Mitsutake Norisato, Hara Yuichiro, Kato Kohji, Mizuno Seiji, Miyake Noriko, Kawai Yosuke, Tokunaga Katsushi, Nagasaki Masao, Kito Seiji, Isoyama Keiichi, Onodera Masafumi, Kaneko Hideo, Matsumoto Naomichi, Matsuda Fumihiko, Matsuo Keitaro, Takahashi Yoshiyuki, Mashimo Tomoji, Kojima Seiji, Ogi Tomoo

    SCIENCE ADVANCES   Vol. 6 ( 51 )   2020.12

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    Publishing type:Research paper (scientific journal)   Publisher:Science Advances  

    DOI: 10.1126/sciadv.abd7197

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  19. Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction

    Konishi Hiroyuki, Okamoto Takayuki, Hara Yuichiro, Komine Okiru, Tamada Hiromi, Maeda Mitsuyo, Osako Fumika, Kobayashi Masaaki, Nishiyama Akira, Kataoka Yosky, Takai Toshiyuki, Udagawa Nobuyuki, Jung Steffen, Ozato Keiko, Tamura Tomohiko, Tsuda Makoto, Yamanaka Koji, Ogi Tomoo, Sato Katsuaki, Kiyama Hiroshi

    EMBO JOURNAL   Vol. 39 ( 22 ) page: e104464   2020.11

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    DOI: 10.15252/embj.2020104464

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  20. A heterozygous SERPINB7 mutation is a possible modifying factor for epidermolytic palmoplantar keratoderma.

    Yoshikawa T, Takeichi T, Ogi T, Suga Y, Muro Y, Akiyama M

    Journal of dermatological science   Vol. 100 ( 2 ) page: 148 - 151   2020.11

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    DOI: 10.1016/j.jdermsci.2020.05.001

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  21. Comprehensive pathogen detection in sera of Kawasaki disease patients by high-throughput sequencing: a retrospective exploratory study

    Torii Yuka, Horiba Kazuhiro, Hayano Satoshi, Kato Taichi, Suzuki Takako, Kawada Jun-ichi, Takahashi Yoshiyuki, Kojima Seiji, Okuno Yusuke, Ogi Tomoo, Ito Yoshinori

    BMC PEDIATRICS   Vol. 20 ( 1 ) page: 482   2020.10

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    DOI: 10.1186/s12887-020-02380-7

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  22. Gene Expression Profile at the Motor Endplate of the Neuromuscular Junction of Fast-Twitch Muscle

    Huang Kun, Li Jin, Ito Mikako, Takeda Jun-Ichi, Ohkawara Bisei, Ogi Tomoo, Masuda Akio, Ohno Kinji

    FRONTIERS IN MOLECULAR NEUROSCIENCE   Vol. 13   page: 154   2020.9

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    DOI: 10.3389/fnmol.2020.00154

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  23. NUS1 mutation in a family with epilepsy, cerebellar ataxia, and tremor. Reviewed International journal

    Kunihiko Araki, Ryoichi Nakamura, Daisuke Ito, Kohji Kato, Yohei Iguchi, Kentaro Sahashi, Miho Toyama, Kensuke Hamada, Nobuhiko Okamoto, Yoshinao Wada, Tomohiko Nakamura, Tomoo Ogi, Masahisa Katsuno

    Epilepsy research   Vol. 164   page: 106371 - 106371   2020.8

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    We report on familial 5 epilepsy patients with autosomal dominant inheritance of a novel heterozygous NUS1 frameshift mutation. All patients had cerebellar ataxia and tremor. Three patients were diagnosed with childhood absence epilepsy, 1 patient with generalized epilepsy, and 1 patient with parkinsonism without epilepsy. Our cases and previously reported cases with deletions of chromosome 6q22 that include NUS1 share these common symptoms. In a cellular experiment, NUS1 mutation led to a substantial reduction of the protein level of NUS1. NUS1 mutation could contribute to epilepsy pathogenesis and also constitute a distinct syndromic entity with cerebellar ataxia and tremor.

    DOI: 10.1016/j.eplepsyres.2020.106371

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  24. Topoisomerase I-driven repair of UV-induced damage in NER-deficient cells. Reviewed International journal

    Liton Kumar Saha, Mitsuo Wakasugi, Salma Akter, Rajendra Prasad, Samuel H Wilson, Naoto Shimizu, Hiroyuki Sasanuma, Shar-Yin Naomi Huang, Keli Agama, Yves Pommier, Tsukasa Matsunaga, Kouji Hirota, Shigenori Iwai, Yuka Nakazawa, Tomoo Ogi, Shunichi Takeda

    Proceedings of the National Academy of Sciences of the United States of America   Vol. 117 ( 25 ) page: 14412 - 14420   2020.6

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    Nucleotide excision repair (NER) removes helix-destabilizing adducts including ultraviolet (UV) lesions, cyclobutane pyrimidine dimers (CPDs), and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). In comparison with CPDs, 6-4PPs have greater cytotoxicity and more strongly destabilizing properties of the DNA helix. It is generally believed that NER is the only DNA repair pathway that removes the UV lesions as evidenced by the previous data since no repair of UV lesions was detected in NER-deficient skin fibroblasts. Topoisomerase I (TOP1) constantly creates transient single-strand breaks (SSBs) releasing the torsional stress in genomic duplex DNA. Stalled TOP1-SSB complexes can form near DNA lesions including abasic sites and ribonucleotides embedded in chromosomal DNA. Here we show that base excision repair (BER) increases cellular tolerance to UV independently of NER in cancer cells. UV lesions irreversibly trap stable TOP1-SSB complexes near the UV damage in NER-deficient cells, and the resulting SSBs activate BER. Biochemical experiments show that 6-4PPs efficiently induce stable TOP1-SSB complexes, and the long-patch repair synthesis of BER removes 6-4PPs downstream of the SSB. Furthermore, NER-deficient cancer cell lines remove 6-4PPs within 24 h, but not CPDs, and the removal correlates with TOP1 expression. NER-deficient skin fibroblasts weakly express TOP1 and show no detectable repair of 6-4PPs. Remarkably, the ectopic expression of TOP1 in these fibroblasts led them to completely repair 6-4PPs within 24 h. In conclusion, we reveal a DNA repair pathway initiated by TOP1, which significantly contributes to cellular tolerance to UV-induced lesions particularly in malignant cancer cells overexpressing TOP1.

    DOI: 10.1073/pnas.1920165117

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  25. InMeRF: prediction of pathogenicity of missense variants by individual modeling for each amino acid substitution

    Takeda Jun-ichi, Nanatsue Kentaro, Yamagishi Ryosuke, Ito Mikako, Haga Nobuhiko, Hirata Hiromi, Ogi Tomoo, Ohno Kinji

    NAR GENOMICS AND BIOINFORMATICS   Vol. 2 ( 2 ) page: lqaa038   2020.6

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    DOI: 10.1093/nargab/lqaa038

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  26. Ubiquitination of DNA Damage-Stalled RNAPII Promotes Transcription-Coupled Repair. Reviewed International journal

    Yuka Nakazawa, Yuichiro Hara, Yasuyoshi Oka, Okiru Komine, Diana van den Heuvel, Chaowan Guo, Yasukazu Daigaku, Mayu Isono, Yuxi He, Mayuko Shimada, Kana Kato, Nan Jia, Satoru Hashimoto, Yuko Kotani, Yuka Miyoshi, Miyako Tanaka, Akira Sobue, Norisato Mitsutake, Takayoshi Suganami, Akio Masuda, Kinji Ohno, Shinichiro Nakada, Tomoji Mashimo, Koji Yamanaka, Martijn S Luijsterburg, Tomoo Ogi

    Cell   Vol. 180 ( 6 ) page: 1228 - +   2020.3

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    Transcription-coupled nucleotide excision repair (TC-NER) is initiated by the stalling of elongating RNA polymerase II (RNAPIIo) at DNA lesions. The ubiquitination of RNAPIIo in response to DNA damage is an evolutionarily conserved event, but its function in mammals is unknown. Here, we identified a single DNA damage-induced ubiquitination site in RNAPII at RPB1-K1268, which regulates transcription recovery and DNA damage resistance. Mechanistically, RPB1-K1268 ubiquitination stimulates the association of the core-TFIIH complex with stalled RNAPIIo through a transfer mechanism that also involves UVSSA-K414 ubiquitination. We developed a strand-specific ChIP-seq method, which revealed RPB1-K1268 ubiquitination is important for repair and the resolution of transcriptional bottlenecks at DNA lesions. Finally, RPB1-K1268R knockin mice displayed a short life-span, premature aging, and neurodegeneration. Our results reveal RNAPII ubiquitination provides a two-tier protection mechanism by activating TC-NER and, in parallel, the processing of DNA damage-stalled RNAPIIo, which together prevent prolonged transcription arrest and protect against neurodegeneration.

    DOI: 10.1016/j.cell.2020.02.010

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  27. Severe achondroplasia due to two de novo variants in the transmembrane domain of FGFR3 on the same allele: A case report. Reviewed International journal

    Tadashi Nagata, Masaki Matsushita, Kenichi Mishima, Yasunari Kamiya, Kohji Kato, Miho Toyama, Tomoo Ogi, Naoki Ishiguro, Hiroshi Kitoh

    Molecular genetics & genomic medicine   Vol. 8 ( 3 ) page: e1148   2020.3

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    BACKGROUND: Achondroplasia (ACH), the most common form of short-limbed skeletal dysplasia, is caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. More than 97% of patients result from a heterozygous p.G380R mutation in the FGFR3 gene. We present here a child who had two de novo variants in the FGFR3 on the same allele, a common p.G380R mutation and a novel p.S378N variant. METHODS: A 3-year-old Japanese girl born from non-consanguineous healthy parents showed more severe clinical and radiological phenotypes than classic ACH, including severe short-limbed short stature with marked ossification defects in the metaphysis and epiphysis, hydrocephalus and cervicomedullary compression due to foramen magnum stenosis, prolonged pulmonary hypoplasia, and significant delay in the gross motor development. Genomic DNA was extracted from the proband and whole-exome sequencing was performed. The variants were subsequently confirmed by Sanger sequencing. RESULTS: Mutation analysis demonstrated that the proband had p.S378N (c.1133G>A) and p.G380R (c.1138G>A) variants in the FGFR3 gene. Both variants were not detected in her parents and therefore considered de novo. An allele-specific PCR was developed in order to determine whether these mutations were on the same allele (cis) or on different alleles (trans). The c.1138G>A mutation was found in the PCR product generated with the primer for the mutant 1133A, but it was not detected in the product with the wild-type 1133G, confirming that p.S378N and p.G380R variants were located on the same allele (cis). CONCLUSION: This is the second case who had two FGFR3 variants in the transmembrane domain on the same allele. The p.S378N variant may provide an additive effect on the activating receptor with the p.G380R mutation and alter the protein function, which could be responsible for the severe phenotype of the present case.

    DOI: 10.1002/mgg3.1148

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  28. Reduced stratum corneum acylceramides in autosomal recessive congenital ichthyosis with a NIPAL4 mutation. Reviewed International journal

    Yuya Murase, Takuya Takeichi, Akane Kawamoto, Kana Tanahashi, Yusuke Okuno, Hiroyuki Takama, Eri Shimizu, Junko Ishikawa, Tomoo Ogi, Masashi Akiyama

    Journal of dermatological science   Vol. 97 ( 1 ) page: 50 - 56   2020.1

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    BACKGROUND: NIPAL4, encoding the NIPA-like domain containing 4 protein (NIPAL4), is one of the causative genes of autosomal recessive congenital ichthyosis (ARCI). The physiological role of NIPAL4 and the pathogenetic mechanisms of ARCI caused by NIPAL4 mutations remain unclear. OBJECTIVE: To clarify the changes of ceramide components in the lesional stratum corneum (SC) and the gene expression profile in the lesional skin of an ARCI patient with a novel frameshift mutation in NIPAL4. METHODS: We performed ultrastructural and immunohistochemical analyses of the skin. We used RNA sequencing to determine the mRNA expression in the skin of the patient and healthy individuals. We investigated ceramide components using tape stripped SC samples from the patient. RESULTS: mRNA expression profiling in the patient's skin showed significant upregulation of IL-17/TNFα-related genes (IL17C, IL36A, IL36G, S100A7A, S100A9) and psoriasis hallmark genes (VNN3, LCE3D, PLA2G4D), and significant downregulation of lipid-associated genes (GAL, HAO2, FABP7). Ceramide analysis in the patient's SC revealed amounts of CER[NS] with carbon chain-length (C) 32-52 were increased, while amounts of most acylceramide with C66:2 - C72:2 were reduced relatively to those in healthy individuals. After the retinoid treatment, CER[NS] with carbon chains C46-54, CER[EOH] and CER[EOP] increased. CONCLUSION: IL-17C and IL-36 family cytokines might be involved in the pathogenetic process of ARCI with NIPAL4 mutations. Reduced amounts of the acylceramides in the SC are associated with the skin phenotype due to NIPAL4 mutations. Efficacy of the oral retinoid treatment might be due to restored amounts of CER[EOH] and CER[EOP] in the SC.

    DOI: 10.1016/j.jdermsci.2019.12.001

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  29. Whole Exome Sequencing Contributes to Genetic Diagnosis of IBMFS Patients

    Muramatsu Hideki, Hamada Motoharu, Okuno Yusuke, Wakamatsu Manabu, Taniguchi Rieko, Narita Koutarou, Kawashima Nozomu, Kitazawa Hironobu, Ichikawa Daisuke, Nishikawa Eri, Kawashima Nazomu, Narita Atsushi, Nishio Nobuhiro, Kojima Seiji, Ogi Tomoo, Takahashi Yoshiyuki

    PEDIATRIC BLOOD & CANCER   Vol. 66   page: S63 - S64   2019.12

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  30. Whole Exome Sequencing Contributes to Genetic Diagnosis of IBMFS Patients

    Muramatsu Hideki, Hamada Motoharu, Okuno Yusuke, Wakamatsu Manabu, Taniguchi Rieko, Narita Koutarou, Kawashima Nozomu, Kitazawa Hironobu, Ichikawa Daisuke, Nishikawa Eri, Kawashima Nazomu, Narita Atsushi, Nishio Nobuhiro, Kojima Seiji, Ogi Tomoo, Takahashi Yoshiyuki

    PEDIATRIC BLOOD & CANCER   Vol. 66   page: S63-S64   2019.12

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  31. Comprehensive Mutational Analysis of Juvenile Myelomonocytic Leukemia Using Whole-Genome Sequencing

    Okuno Yusuke, Muramatsu Hideki, Murakami Norihiro, Kawashima Nozomu, Wakamatsu Manabu, Kitazawa Hironobu, Ogi Tomoo, Takahashi Yoshiyuki

    BLOOD   Vol. 134   2019.11

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    DOI: 10.1182/blood-2019-121681

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  32. Biallelic VPS35L pathogenic variants cause 3C/Ritscher-Schinzel-like syndrome through dysfunction of retriever complex.

    Kato K, Oka Y, Muramatsu H, Vasilev FF, Otomo T, Oishi H, Kawano Y, Kidokoro H, Nakazawa Y, Ogi T, Takahashi Y, Saitoh S

    Journal of medical genetics     2019.11

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    DOI: 10.1136/jmedgenet-2019-106213

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  33. A novel NCSTN missense mutation in the signal peptide domain causes hidradenitis suppurativa, which has features characteristic of an autoinflammatory keratinization disease

    Takeichi T., Matsumoto T., Nomura T., Takeda M., Niwa H., Kono M., Shimizu H., Ogi T., Akiyama M.

    BRITISH JOURNAL OF DERMATOLOGY     2019.10

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    DOI: 10.1111/bjd.18445

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  34. Hailey-Hailey disease with oesophageal involvement due to a previously unreported ATP2C1 mutation. Reviewed International journal

    Michihiro Kono, Masanari Kodera, Yu Inasaka, Izumi Hasegawa, Yoshinao Muro, Yuka Nakazawa, Tomoo Ogi, Masashi Akiyama

    European journal of dermatology : EJD   Vol. in press   2019.8

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    DOI: 10.1684/ejd.2019.3507

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  35. Bi-allelic TARS Mutations Are Associated with Brittle Hair Phenotype

    Thei Arjan F., Botta Elena, Raams Anja, Smith Desiree E. C., Mendes Marisa I, Caligiuri Giuseppina, Giachetti Sarah, Bione Silvia, Carriero Roberta, Liberi Giordano, Zardoni Luca, Swagemakers Sigrid M. A., Salomons Gajja S., Sarasin Alain, Lehmann Alan, van der Spek Peter J., Ogi Tomoo, Hoeijmakers Jan H. J., Vermeulen Wim, orioli Donata

    AMERICAN JOURNAL OF HUMAN GENETICS   Vol. 105 ( 2 ) page: 434-440   2019.8

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    DOI: 10.1016/j.ajhg.2019.06.017

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  36. Unravelling the pivotal role of DDA1 in transcription-coupled nucleotide excision repair

    Pines A., Guo C., Akita M., Theil A., Quist B., Wienholz F., Marteijn J., Demmers J., van Attikum H., Vertegaal A., Vermeulen M., Ogi T., Vermeulen W.

    BRITISH JOURNAL OF DERMATOLOGY   Vol. 180 ( 6 ) page: E230 - E230   2019.6

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  37. Unravelling the pivotal role of DDA1 in transcription-coupled nucleotide excision repair

    Pines A, Guo C, Akita M, Theil A, Quist B, Wienholz F, Marteijn J, Demmers J, van Attikum H, Vertegaal A, Vermeulen M, Ogi T, Vermeulen W

    BRITISH JOURNAL OF DERMATOLOGY   Vol. 180 ( 6 ) page: E230-E230   2019.6

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  38. JAK/STAT3 and NF-κB Signaling Pathways Regulate Cancer Stem-Cell Properties in Anaplastic Thyroid Cancer Cells Reviewed

    Ken Shiraiwa, Michiko Matsuse, Yuka Nakazawa, Tomoo Ogi, Keiji Suzuki, Vladimir Saenko, Shuhang Xu, Kazuo Umezawa, Shunichi Yamashita, Kazuhiro Tsukamoto, Norisato Mitsutake

    Thyroid   Vol. 29 ( 5 ) page: 674 - 682   2019.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Mary Ann Liebert Inc  

    DOI: 10.1089/thy.2018.0212

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    Other Link: https://www.liebertpub.com/doi/pdf/10.1089/thy.2018.0212

  39. A Japanese Case of Galli-Galli Disease due to a Previously Unreported POGLUT1 Mutation

    Kono Michihiro, Sawada Masaki, Nakazawa Yuka, Ogi Tomoo, Muro Yoshinao, Akiyama Masashi

    ACTA DERMATO-VENEREOLOGICA   Vol. 99 ( 4 ) page: 458-459   2019.4

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    DOI: 10.2340/00015555-3119

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  40. Functional Comparison of XPF Missense Mutations Associated to Multiple DNA Repair Disorders

    Marin Maria, Jose Ramirez Maria, Carmona Miriam Aza, Jia Nan, Ogi Tomoo, Bogliolo Massimo, Surralles Jordi

    GENES   Vol. 10 ( 1 )   2019.1

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    DOI: 10.3390/genes10010060

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  41. Functional and clinical relevance of novel mutations in a large cohort of patients with Cockayne syndrome

    Calmels Nadege, Botta Elena, Jia Nan, Fawcett Heather, Nardo Tiziana, Nakazawa Yuka, Lanzafame Manuela, Moriwaki Shinichi, Sugita Katsuo, Kubota Masaya, Obringer Cathy, Spitz Marie-Aude, Stefanini Miria, Laugel Vincent, Orioli Donata, Ogi Tomoo, Lehmann Alan Robert

    JOURNAL OF MEDICAL GENETICS   Vol. 55 ( 5 ) page: 329-343   2018.5

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    DOI: 10.1136/jmedgenet-2017-104877

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  42. Erratum: Author Correction: Phosphorylated HBO1 at UV irradiated sites is essential for nucleotide excision repair (Nature communications (2017) 8 (16102)) Reviewed

    Niida H, Matsunuma R, Horiguchi R, Uchida C, Nakazawa Y, Motegi A, Nishimoto K, Sakai S, Ohhata T, Kitagawa K, Moriwaki S, Nishitani H, Ui A, Ogi T, Kitagawa M

    Nature communications   Vol. 9   page: 16214   2018.4

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    DOI: 10.1038/ncomms16214

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    Other Link: http://orcid.org/0000-0002-5492-9072

  43. An adolescent case of xeroderma pigmentosum variant confirmed by the onset of sun exposure-related skin cancer during Crohn's disease treatment

    Terada Aoi, Aoshima Masahiro, Tanizaki Hideaki, Nakazawa Yuka, Ogi Tomoo, Tokura Yoshiki, Moriwaki Shinichi

    JOURNAL OF CUTANEOUS IMMUNOLOGY AND ALLERGY   Vol. 1 ( 1 ) page: 23-26   2018.4

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/cia2.12011

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  44. Whole exome sequencing of 14 schizophrenia multiplex families in Japan

    Toyama Miho, Takasaki Yuto, Aleksic Branko, Ogi Tomoo, Ozaki Norio

    HUMAN GENOMICS   Vol. 12   page: .   2018.3

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  45. Whole exome sequencing of 14 schizophrenia multiplex families in Japan Reviewed

    Toyama Miho, Takasaki Yuto, Aleksic Branko, Ogi Tomoo, Ozaki Norio

    HUMAN GENOMICS   Vol. 12   2018.3

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  46. Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites

    Yasuda Takeshi, Kagawa Wataru, Ogi Tomoo, Kato Takamitsu A., Suzuki Takehiro, Dohmae Naoshi, Takizawa Kazuya, Nakazawa Yuka, Genet Matthew D., Saotome Mika, Hama Michio, Konishi Teruaki, Nakajima Nakako Izumi, Hazawa Masaharu, Tomita Masanori, Koike Manabu, Noshiro Katsuko, Tomiyama Kenichi, Obara Chizuka, Gotoh Takaya, Ui Ayako, Fujimori Akira, Nakayama Fumiaki, Hanaoka Fumio, Sugasawa Kaoru, Okayasu Ryuichi, Jeggo Penny A., Tajima Katsushi

    PLOS GENETICS   Vol. 14 ( 3 ) page: e1007277   2018.3

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    DOI: 10.1371/journal.pgen.1007277

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  47. Cerebellar ataxia-dominant phenotype in patients with ERCC4 mutations.

    Doi H, Koyano S, Miyatake S, Nakajima S, Nakazawa Y, Kunii M, Tomita-Katsumoto A, Oda K, Yamaguchi Y, Fukai R, Ikeda S, Kato R, Ogata K, Kubota S, Hayashi N, Takahashi K, Tada M, Tanaka K, Nakashima M, Tsurusaki Y, Miyake N, Saitsu H, Ogi T, Aihara M, Takeuchi H, Matsumoto N, Tanaka F

    Journal of human genetics     2018.2

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    DOI: 10.1038/s10038-017-0408-5

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  48. Disorders with deficiency in TC-NER: Molecular pathogenesis of cockayne syndrome and UV-Sensitive syndrome

    Guo C.

    DNA Repair Disorders     page: 25-40   2018.1

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    DOI: 10.1007/978-981-10-6722-8_2

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  49. Common TFIIH recruitment mechanism in global genome and transcription-coupled repair subpathways

    Okuda Masahiko, Nakazawa Yuka, Guo Chaowan, Ogi Tomoo, Nishimura Yoshifumi

    NUCLEIC ACIDS RESEARCH   Vol. 45 ( 22 ) page: 13043-13055   2017.12

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/nar/gkx970

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  50. ALC1/CHD1L, a chromatin-remodeling enzyme, is required for efficient base excision repair

    Tsuda Masataka, Cho Kosai, Ooka Masato, Shimizu Naoto, Watanabe Reiko, Yasui Akira, Nakazawa Yuka, Ogi Tomoo, Harada Hiroshi, Agama Keli, Nakamura Jun, Asada Ryuta, Fujiike Haruna, Sakuma Tetsushi, Yamamoto Takashi, Murai Junko, Hiraoka Masahiro, Koike Kaoru, Pommier Yves, Takeda Shunichi, Hirota Kouji

    PLOS ONE   Vol. 12 ( 11 ) page: e0188320   2017.11

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    DOI: 10.1371/journal.pone.0188320

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  51. Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells

    Doi Ryoichiro, Tsuchiya Tomoshi, Mitsutake Norisato, Nishimura Satoshi, Matsuu-Matsuyama Mutsumi, Nakazawa Yuka, Ogi Tomoo, Akita Sadanori, Yukawa Hiroshi, Baba Yoshinobu, Yamasaki Naoya, Matsumoto Keitaro, Miyazaki Takuro, Kamohara Ryotaro, Hatachi Go, Sengyoku Hideyori, Watanabe Hironosuke, Obata Tomohiro, Niklason Laura E., Nagayasu Takeshi

    SCIENTIFIC REPORTS   Vol. 7 ( 1 ) page: 8447   2017.8

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    DOI: 10.1038/s41598-017-09115-2

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  52. Phosphorylated HBO1 at UV irradiated sites is essential for nucleotide excision repair

    Niida Hiroyuki, Matsunuma Ryoichi, Horiguchi Ryo, Uchida Chiharu, Nakazawa Yuka, Motegi Akira, Nishimoto Koji, Sakai Satoshi, Ohhata Tatsuya, Kitagawa Kyoko, Moriwaki Shinichi, Nishitani Hideo, Ui Ayako, Ogi Tomoo, Kitagawa Masatoshi

    NATURE COMMUNICATIONS   Vol. 8   page: 16102   2017.7

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    DOI: 10.1038/ncomms16102

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  53. An XPA gene splicing mutation resulting in trace protein expression in an elderly patient with xeroderma pigmentosum group A without neurological abnormalities

    Takahashi Y., Endo Y., Kusaka-Kikushima A., Nakamaura S., Nakazawa Y., Ogi T., Uryu M., Tsuji G., Furue M., Moriwaki S.

    BRITISH JOURNAL OF DERMATOLOGY   Vol. 177 ( 1 ) page: 253-257   2017.7

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    DOI: 10.1111/bjd.15051

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  54. Calcification in dermal fibroblasts from a patient with GGCX syndrome accompanied by upregulation of osteogenic molecules

    Okubo Yumi, Masuyama Ritsuko, Iwanaga Akira, Koike Yuta, Kuwatsuka Yutaka, Ogi Tomoo, Yamamoto Yosuke, Endo Yuichiro, Tamura Hiroshi, Utani Atsushi

    PLOS ONE   Vol. 12 ( 5 ) page: e0177375   2017.5

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    DOI: 10.1371/journal.pone.0177375

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  55. PCNA ubiquitylation ensures timely completion of unperturbed DNA replication in fission yeast

    Daigaku Yasukazu, Etheridge Thomas J., Nakazawa Yuka, Nakayama Mayumi, Watson Adam T., Miyabe Izumi, Ogi Tomoo, Osborne Mark A., Carr Antony M.

    PLOS GENETICS   Vol. 13 ( 5 ) page: e1006789   2017.5

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    DOI: 10.1371/journal.pgen.1006789

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  56. Analysis of clinical symptoms and ABCC6 mutations in 76 Japanese patients with pseudoxanthoma elasticum. Reviewed

    Iwanaga A, Okubo Y, Yozaki M, Koike Y, Kuwatsuka Y, Tomimura S, Yamamoto Y, Tamura H, Ikeda S, Maemura K, Tsuiki E, Kitaoka T, Endo Y, Mishima H, Yoshiura KI, Ogi T, Tanizaki H, Wataya-Kaneda M, Hattori T, Utani A

    The Journal of dermatology     2017.2

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    DOI: 10.1111/1346-8138.13727

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  57. A 10-year follow-up of a child with mild case of xeroderma pigmentosum complementation group D diagnosed by whole-genome sequencing. Reviewed

    Ono R, Masaki T, Mayca Pozo F, Nakazawa Y, Swagemakers SM, Nakano E, Sakai W, Takeuchi S, Kanda F, Ogi T, van der Spek PJ, Sugasawa K, Nishigori C

    Photodermatology, photoimmunology & photomedicine   Vol. 32 ( 4 ) page: 174-80   2016.7

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    DOI: 10.1111/phpp.12240

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  58. Novel compound heterozygous DNA ligase IV mutations in an adolescent with a slowly-progressing radiosensitive-severe combined immunodeficiency.

    Tamura S, Higuchi K, Tamaki M, Inoue C, Awazawa R, Mitsuki N, Nakazawa Y, Mishima H, Takahashi K, Kondo O, Imai K, Morio T, Ohara O, Ogi T, Furukawa F, Inoue M, Yoshiura K, Kanazawa N

    Clinical immunology (Orlando, Fla.)   Vol. 160 ( 2 ) page: 255-60   2015.10

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    DOI: 10.1016/j.clim.2015.07.004

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  59. XRCC4 deficiency in human subjects causes a marked neurological phenotype but no overt immunodeficiency.

    The Journal of allergy and clinical immunology   Vol. 136 ( 4 ) page: 1007-17   2015.10

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    DOI: 10.1016/j.jaci.2015.06.007

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  60. SETDB1, HP1 and SUV39 promote repositioning of 53BP1 to extend resection during homologous recombination in G2 cells.

    Alagoz M, Katsuki Y, Ogiwara H, Ogi T, Shibata A, Kakarougkas A, Jeggo P

    Nucleic acids research   Vol. 43 ( 16 ) page: 7931-44   2015.9

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    DOI: 10.1093/nar/gkv722

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  61. Sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells in mice.

    Guo CY, Luo L, Urata Y, Goto S, Huang WJ, Takamura S, Hayashi F, Doi H, Kitajima Y, Ono Y, Ogi T, Li TS

    Scientific reports   Vol. 5   page: 8055   2015.1

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    DOI: 10.1038/srep08055

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  62. A rapid, comprehensive system for assaying DNA repair activity and cytotoxic effects of DNA-damaging reagents.

    Jia N, Nakazawa Y, Guo C, Shimada M, Sethi M, Takahashi Y, Ueda H, Nagayama Y, Ogi T

    Nature protocols   Vol. 10 ( 1 ) page: 12-24   2015.1

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    DOI: 10.1038/nprot.2014.194

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  63. Hypomorphic PCNA mutation underlies a human DNA repair disorder.

    Baple EL, Chambers H, Cross HE, Fawcett H, Nakazawa Y, Chioza BA, Harlalka GV, Mansour S, Sreekantan-Nair A, Patton MA, Muggenthaler M, Rich P, Wagner K, Coblentz R, Stein CK, Last JI, Taylor AM, Jackson AP, Ogi T, Lehmann AR, Green CM, Crosby AH

    The Journal of clinical investigation   Vol. 124 ( 7 ) page: 3137-46   2014.7

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    DOI: 10.1172/JCI74593

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  64. PRKDC mutations in a SCID patient with profound neurological abnormalities.

    Woodbine L, Neal JA, Sasi NK, Shimada M, Deem K, Coleman H, Dobyns WB, Ogi T, Meek K, Davies EG, Jeggo PA

    The Journal of clinical investigation   Vol. 123 ( 7 ) page: 2969-80   2013.7

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    DOI: 10.1172/JCI67349

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  65. Malfunction of nuclease ERCC1-XPF results in diverse clinical manifestations and causes Cockayne syndrome, xeroderma pigmentosum, and Fanconi anemia.

    Kashiyama K, Nakazawa Y, Pilz DT, Guo C, Shimada M, Sasaki K, Fawcett H, Wing JF, Lewin SO, Carr L, Li TS, Yoshiura K, Utani A, Hirano A, Yamashita S, Greenblatt D, Nardo T, Stefanini M, McGibbon D, Sarkany R, Fassihi H, Takahashi Y, Nagayama Y, Mitsutake N, Lehmann AR, Ogi T

    American journal of human genetics   Vol. 92 ( 5 ) page: 807-19   2013.5

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    DOI: 10.1016/j.ajhg.2013.04.007

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  66. [Molecular cloning and characterisation of UVSSA, the responsible gene for UV-sensitive syndrome].

    Ogi T, Nakazawa Y, Sasaki K, Guo C, Yoshiura K, Utani A, Nagayama Y

    Seikagaku. The Journal of Japanese Biochemical Society   Vol. 85 ( 3 ) page: 133-44   2013.3

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  67. Functional characterization of the novel BRAF complex mutation, BRAF(V600delinsYM) , identified in papillary thyroid carcinoma.

    Matsuse M, Mitsutake N, Tanimura S, Ogi T, Nishihara E, Hirokawa M, Fuziwara CS, Saenko VA, Suzuki K, Miyauchi A, Yamashita S

    International journal of cancer. Journal international du cancer   Vol. 132 ( 3 ) page: 738-43   2013.2

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    DOI: 10.1002/ijc.27709

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  68. miR-196a downregulation increases the expression of type I and III collagens in keloid fibroblasts.

    Kashiyama K, Mitsutake N, Matsuse M, Ogi T, Saenko VA, Ujifuku K, Utani A, Hirano A, Yamashita S

    The Journal of investigative dermatology   Vol. 132 ( 6 ) page: 1597-604   2012.6

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    DOI: 10.1038/jid.2012.22

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  69. Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair.

    Nakazawa Y, Sasaki K, Mitsutake N, Matsuse M, Shimada M, Nardo T, Takahashi Y, Ohyama K, Ito K, Mishima H, Nomura M, Kinoshita A, Ono S, Takenaka K, Masuyama R, Kudo T, Slor H, Utani A, Tateishi S, Yamashita S, Stefanini M, Lehmann AR, Yoshiura K, Ogi T

    Nature genetics   Vol. 44 ( 5 ) page: 586-92   2012.5

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    DOI: 10.1038/ng.2229

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  70. Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome.

    Ogi T, Walker S, Stiff T, Hobson E, Limsirichaikul S, Carpenter G, Prescott K, Suri M, Byrd PJ, Matsuse M, Mitsutake N, Nakazawa Y, Vasudevan P, Barrow M, Stewart GS, Taylor AM, O'Driscoll M, Jeggo PA

    PLoS genetics   Vol. 8 ( 11 ) page: e1002945   2012

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    DOI: 10.1371/journal.pgen.1002945

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  71. Two unrelated patients with MRE11A mutations and Nijmegen breakage syndrome-like severe microcephaly.

    Matsumoto Y, Miyamoto T, Sakamoto H, Izumi H, Nakazawa Y, Ogi T, Tahara H, Oku S, Hiramoto A, Shiiki T, Fujisawa Y, Ohashi H, Sakemi Y, Matsuura S

    DNA repair   Vol. 10 ( 3 ) page: 314-21   2011.3

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    DOI: 10.1016/j.dnarep.2010.12.002

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  72. A semi-automated non-radioactive system for measuring recovery of RNA synthesis and unscheduled DNA synthesis using ethynyluracil derivatives.

    Nakazawa Y, Yamashita S, Lehmann AR, Ogi T

    DNA repair   Vol. 9 ( 5 ) page: 506-16   2010.5

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    DOI: 10.1016/j.dnarep.2010.01.015

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  73. Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells.

    Ogi T, Limsirichaikul S, Overmeer RM, Volker M, Takenaka K, Cloney R, Nakazawa Y, Niimi A, Miki Y, Jaspers NG, Mullenders LH, Yamashita S, Fousteri MI, Lehmann AR

    Molecular cell   Vol. 37 ( 5 ) page: 714-27   2010.3

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    DOI: 10.1016/j.molcel.2010.02.009

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  74. Collaborative action of Brca1 and CtIP in elimination of covalent modifications from double-strand breaks to facilitate subsequent break repair.

    Nakamura K, Kogame T, Oshiumi H, Shinohara A, Sumitomo Y, Agama K, Pommier Y, Tsutsui KM, Tsutsui K, Hartsuiker E, Ogi T, Takeda S, Taniguchi Y

    PLoS genetics   Vol. 6 ( 1 ) page: e1000828   2010.1

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    DOI: 10.1371/journal.pgen.1000828

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  75. A rapid non-radioactive technique for measurement of repair synthesis in primary human fibroblasts by incorporation of ethynyl deoxyuridine (EdU).

    Limsirichaikul S, Niimi A, Fawcett H, Lehmann A, Yamashita S, Ogi T

    Nucleic acids research   Vol. 37 ( 4 ) page: e31   2009.3

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    DOI: 10.1093/nar/gkp023

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  76. Translesion synthesis: Y-family polymerases and the polymerase switch.

    Lehmann AR, Niimi A, Ogi T, Brown S, Sabbioneda S, Wing JF, Kannouche PL, Green CM

    DNA repair   Vol. 6 ( 7 ) page: 891-9   2007.7

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    DOI: 10.1016/j.dnarep.2007.02.003

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  77. Differential Bvg phase-dependent regulation and combinatorial role in pathogenesis of two Bordetella paralogs, BipA and BcfA.

    Sukumar N, Mishra M, Sloan GP, Ogi T, Deora R

    Journal of bacteriology   Vol. 189 ( 10 ) page: 3695-704   2007.5

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    DOI: 10.1128/JB.00009-07

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  78. The Y-family DNA polymerase kappa (pol kappa) functions in mammalian nucleotide-excision repair.

    Ogi T, Lehmann AR

    Nature cell biology   Vol. 8 ( 6 ) page: 640-2   2006.6

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    DOI: 10.1038/ncb1417

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  79. Involvement of vertebrate Polkappa in translesion DNA synthesis across DNA monoalkylation damage.

    Takenaka K, Ogi T, Okada T, Sonoda E, Guo C, Friedberg EC, Takeda S

    The Journal of biological chemistry   Vol. 281 ( 4 ) page: 2000-4   2006.1

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    DOI: 10.1074/jbc.M506153200

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  80. Binding and transcriptional activation of non-flagellar genes by the Escherichia coli flagellar master regulator FlhD2C2.

    Stafford GP, Ogi T, Hughes C

    Microbiology (Reading, England)   Vol. 151 ( Pt 6 ) page: 1779-88   2005.6

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    DOI: 10.1099/mic.0.27879-0

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  81. Up-regulation of the error-prone DNA polymerase {kappa} promotes pleiotropic genetic alterations and tumorigenesis.

    Bavoux C, Leopoldino AM, Bergoglio V, O-Wang J, Ogi T, Bieth A, Judde JG, Pena SD, Poupon MF, Helleday T, Tagawa M, Machado C, Hoffmann JS, Cazaux C

    Cancer research   Vol. 65 ( 1 ) page: 325-30   2005.1

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  82. Localisation of human Y-family DNA polymerase kappa: relationship to PCNA foci.

    Ogi T, Kannouche P, Lehmann AR

    Journal of cell science   Vol. 118 ( Pt 1 ) page: 129-36   2005.1

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    DOI: 10.1242/jcs.01603

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  83. Elevated expression of DNA polymerase kappa in human lung cancer is associated with p53 inactivation: Negative regulation of POLK promoter activity by p53.

    Wang Y, Seimiya M, Kawamura K, Yu L, Ogi T, Takenaga K, Shishikura T, Nakagawara A, Sakiyama S, Tagawa M, O-Wang J

    International journal of oncology   Vol. 25 ( 1 ) page: 161-5   2004.7

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  84. Mammalian Pol kappa: regulation of its expression and lesion substrates.

    Ohmori H, Ohashi E, Ogi T

    Advances in protein chemistry   Vol. 69   page: 265-78   2004

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    DOI: 10.1016/S0065-3233(04)69009-7

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  85. The absence of DNA polymerase kappa does not affect somatic hypermutation of the mouse immunoglobulin heavy chain gene.

    Shimizu T, Shinkai Y, Ogi T, Ohmori H, Azuma T

    Immunology letters   Vol. 86 ( 3 ) page: 265-70   2003.5

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  86. Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis.

    Schuster M, Lostroh CP, Ogi T, Greenberg EP

    Journal of bacteriology   Vol. 185 ( 7 ) page: 2066-79   2003.4

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  87. Polkappa protects mammalian cells against the lethal and mutagenic effects of benzo[a]pyrene.

    Ogi T, Shinkai Y, Tanaka K, Ohmori H

    Proceedings of the National Academy of Sciences of the United States of America   Vol. 99 ( 24 ) page: 15548-53   2002.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1073/pnas.222377899

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  88. [Biochemical studies of human DNA polymerase kappa and its transcriptional regulation].

    Ohashi E, Ogi T, Ohmori H

    Seikagaku. The Journal of Japanese Biochemical Society   Vol. 74 ( 3 ) page: 218-23   2002.3

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    PubMed

  89. Expression of human and mouse genes encoding polkappa: testis-specific developmental regulation and AhR-dependent inducible transcription.

    Ogi T, Mimura J, Hikida M, Fujimoto H, Fujii-Kuriyama Y, Ohmori H

    Genes to cells : devoted to molecular & cellular mechanisms   Vol. 6 ( 11 ) page: 943-53   2001.11

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    PubMed

  90. [Mutagenesis by Escherichia coli DinB and its mammalian homolog Pol kappa].

    Ogi T, Ohashi E, Ohmori H

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   Vol. 46 ( 8 Suppl ) page: 1155-61   2001.6

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    PubMed

  91. Error-prone bypass of certain DNA lesions by the human DNA polymerase kappa.

    Ohashi E, Ogi T, Kusumoto R, Iwai S, Masutani C, Hanaoka F, Ohmori H

    Genes & development   Vol. 14 ( 13 ) page: 1589-94   2000.7

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    PubMed

  92. Identification of additional genes belonging to the LexA regulon in Escherichia coli.

    Molecular microbiology   Vol. 35 ( 6 ) page: 1560-72   2000.3

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    PubMed

  93. Mutation enhancement by DINB1, a mammalian homologue of the Escherichia coli mutagenesis protein dinB.

    Ogi T, Kato T Jr, Kato T, Ohmori H

    Genes to cells : devoted to molecular & cellular mechanisms   Vol. 4 ( 11 ) page: 607-18   1999.11

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    PubMed

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Presentations 2

  1. RNA polymerase IIのユビキチン化修飾による転写共役修復開始反応の分子機構とその破綻により発症する哺乳類の神経変性のメカニズム

    荻朋男

    第42回日本分子生物学会年会  2019.12.5 

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    Language:English   Presentation type:Oral presentation (invited, special)  

  2. 希少未診断疾患におけるゲノム解析およびデータ評価パイプラインの構築

    中沢由華, 原雄一郎, 遠山美穂, 岡泰由, 荻朋男

    第4回名大医薬系3部局交流シンポジウム  2019.10.31 

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    Language:English   Presentation type:Poster presentation  

Works 17

  1. 紫外線感受性症候群責任因子によるRNAポリメラーゼユビキチン化と待避機構の解析

    2012
    -
    2014

  2. ヌクレオチド除去修復欠損性日光過敏症のウイルス発現系とゲノム解析による網羅的探索

    2012
    -
    2014

  3. 放射線損傷DNA修復過程における複製忠実度の 低いDNAポリメラーゼによる突然変異誘発機構の解析

    2011
    -
    2012

  4. ヌクレオチド除去修復過程における修復DNA合成の分子メカニズムの解明

    2010
    -
    2011

  5. 紫外線DNA損傷修復研究

    2010
    -
    2011

  6. 紫外線DNA損傷修復研究

    2010
    -
    2011

  7. DNA損傷の修復合成過程におけるDNAポリメラーゼの選択機構と、複製エラーを伴うDNA修復による突然変異誘発機構の解明

    2010
    -
    2011

  8. DNA修復過程でのヌクレオシドの取り込みを指標とした不正確な修復合成を誘発するDNA修復因子の探索

    2010
    -
    2011

  9. 放射線DNA損傷の新たな修復メカニズムの解明と放射線誘発がん予防のためのリスク評価

    2009
    -
    2011

  10. DNA損傷修復過程における複製忠実度の低いDNAポリメラーゼの機能解析

    2009
    -
    2010

  11. 化粧品添加物および日光過敏症新薬開発を目的とする光DNA損傷修復遺伝子のスクリーニング

    2009
    -
    2010

  12. 紫外線防護効果の高い化粧品添加物の高速スクリーニング技術の開発

    2009
    -
    2010

  13. 養蜂製品の光DNA損傷修復促進効果に関する基礎的研究と 高機能化粧品添加物としての有用性評価

    2009
    -
    2010

  14. DNA損傷修復過程において複製精度の低いDNAポリメラーゼが選択される仕組みと、DNA修復に起因する突然変異の蓄積に伴う発がんメカニズムの解明

    2009
    -
    2010

  15. DNA修復過程における複製忠実度の低いDNAポリメラーゼの機能解析

    2009
    -
    2010

  16. 放射線損傷DNA修復過程における複製忠実度の 低いDNAポリメラーゼによる突然変異誘発機構の解析

    2009
    -
    2010

  17. 修復DNA合成過程でのポリメラーゼ選択機構と複製忠実度の低いDNAポリメラーゼの作用による突然変異誘発メカニズムの解明

    2009
    -
    2010

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Research Project for Joint Research, Competitive Funding, etc. 7

  1. 中部東海地区IRUDゲノム解析拠点-先端情報技術の融合による包括的遺伝子診断の提供

    2018.3 - 2021.3

    AMED難治性疾患実用化研究事業 

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    Grant type:Competitive

  2. 中部東海地区IRUDゲノム解析拠点-先端情報技術の融合による包括的遺伝子診断の提供

    2018.3 - 2021.3

    AMED難治性疾患実用化研究事業 

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    Grant type:Competitive

  3. ゲノム不安定性疾患群を中心とした希少難治性疾患の次世代マルチオミクス診断拠点構築

    2017.4 - 2020.3

    AMED難治性疾患実用化研究事業 

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    Grant type:Competitive

  4. ゲノム不安定性疾患群を中心とした希少難治性疾患の次世代マルチオミクス診断拠点構築

    2017.4 - 2020.3

    AMED難治性疾患実用化研究事業 

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    Grant type:Competitive

  5. DNA修復・損傷応答機構の異常により発症するゲノム不安定性疾患の分子病態解明研究

    2017.4 - 2020.3

    科学研究費助成事業 

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    Grant type:Competitive

  6. ゲノム不安定性を誘発する先天性稀少疾患と小児がんコホートの分子遺伝疫学調査

    2015.4 - 2018.3

    科学研究費助成事業 

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    Grant type:Competitive

  7. 転写共役ヌクレオチド除去修復開始反応のin vitro再構成

    2014.4 - 2018.3

    科学研究費助成事業 

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    Grant type:Competitive

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KAKENHI (Grants-in-Aid for Scientific Research) 28

  1. ロングリード配列決定法による放射線被ばく刻印の同定

    Grant number:20K21718  2020.7 - 2022.3

    挑戦的研究(萌芽)

    光武 範吏

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    Authorship:Coinvestigator(s) 

    放射線被ばくによって癌が発生するのは明らかであるが、あるひとつの癌が放射線で引き起こされたものか、その他の原因で起きたものかを区別する方法は今のところない。放射線はクラスター損傷と呼ばれる複雑な異常をDNAに引き起こし、マイクロホモロジーを伴う欠失や逆位を生じさせるとされるが、これらを全ゲノムレベルで解析する手法は今までなかった。本研究では、様々な線量の放射線を照射し樹立したHPRT変異細胞クローンと、新規技術であるロングリードシークエンシングを用い、上記の欠失や逆位を全ゲノムレベルで解析し、放射線刻印とも呼べる放射線特異的なゲノム変化の有無を明らかにする。

  2. MYRF遺伝子を起点とした発熱時言動異常の病態解明

    Grant number:20K08241  2020.4 - 2024.3

    倉橋 宏和

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    我が国において、発熱に伴ってうわごとを言うなどの意識障害は稀ではなく、重篤な場合はインフルエンザ感染に伴う異常言動のように社会問題となりえます。MERS(可逆性脳梁膨大部病変を有する軽症脳炎・脳症)は、発熱に伴い異常言動を呈する代表的な急性脳症です。我々は、2家系のMERS家族例においてMYRF遺伝子変異を同定しました。この研究は、MYRF遺伝子に着目して、その遺伝学的背景をより明らかにすること、また、変異MYRFについてモデル動物やモデル細胞を作成し、その特徴を明らかにすることを目的としています。

  3. Molecular pathogenesis of human disorders associated with deficiencies in the DNA repair and environmental stress response systems

    Grant number:20H00629  2020.4 - 2023.3

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    Authorship:Principal investigator 

    Grant amount:\45370000 ( Direct Cost: \34900000 、 Indirect Cost:\10470000 )

  4. DNA損傷部位特異的に集積する転写共役修復因子群を同定・評価する新規技術の開発

    Grant number:19H04266  2019.4 - 2022.3

    橋本 悟

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    RNA合成酵素が転写伸長中にDNA損傷と衝突した際に生じていると考えられている、バックトラッキング(DNA損傷部位から転写と逆方向にRNA合成酵素がスライドする現象)の観察が可能となる新しい実験系を開発する。この実験系を用いて、転写と共役したDNA修復異常を来す各種疾患群の病態メカニズム解明を目指す。
    紫外線によって生じるDNA損傷を修復する機構にヌクレオチド除去修復(NER)が存在する。NERにはゲノム全体を修復する全ゲノム修復(GGR)と、転写伸長中のRNAポリメラーゼII(PolII)がDNA損傷を認識して遺伝子領域だけの修復行う転写共役修復(TCR)とに分けられる。GGRの分子メカニズムは概ね理解されているが、TCRのそれは不明な点が未だ多い。その原因として、生細胞内においてDNA損傷とPolIIが衝突する、ゲノム上における部位特異的な現象を詳細に評価できる実験系が存在しないためである。本研究では、ゲノム上の特定の部位におけるDNA損傷とPolIIの衝突を評価できる実験系の開発を主たる目的とし、併せてNERの異常によって生じる疾患群の病態解明を目指す。
    本年度は、既存技術であるクロマチン免疫沈降法(ChIP)とスロットブロットを融合し、PolIIとDNA損傷の相互作用を解析する手法を確立した。この技術を用いて、現在開発中である新規技術を用いてゲノム上における時間・空間的に制御可能なDNA損傷を誘導できるシステムの検証を行う準備が整った。
    新規技術開発と並行して、各種NER因子を欠損させたHeLa細胞を用いたChIP解析を行い、紫外線照射後におけるPolIIの挙動を確認した。さらに、NERの異常によって生じるTrichothiodystrophy(TTD)のモデルマウス由来の皮膚ケラチノサイトを用いたRNAseq解析を行い、TTDにおける表皮の異常(魚鱗癬)がコレステロールダイナミクスに関連する遺伝子発現異常と相関する事を明らかにした。
    既存技術の融合によって、研究目的である新規技術の開発に必要な評価系を確立する事が可能になったため。
    今後は、新規技術を用いた新しい実験系の条件検討を行う。具体的には、特異的DNA損傷の導入条件を、導入後のDNA損傷の細胞内分布および量を経時的に観察することによって行う。また細胞内に導入した特異的DNA損傷を含む複合体の抽出に挑戦する。またGGRとTCRの二重欠損細胞の作成も予備的にすすめる。

  5. 次世代シークエンスによる包括的な重症感染症リキッドバイオプシー

    Grant number:19K08298  2019.4 - 2022.3

    伊藤 嘉規

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    近年の分子生物学の進展を応用し、侵襲性の少ない、包括的(微生物と生体情報をともに含む)な重症診断法開発の基盤となる研究を行う。病原微生物である、細菌、ウイルス、真菌などは、培養や核酸検出など様々な方法で検出されるが、次世代シークエンスは網羅的な微生物検出が可能である。他方、血液などの体液中には、細胞から分泌されるエクソソーム、Cell-free DNA、マイクロRNAが存在する。これらの微小な細胞由来分子を分離・解析し、重症感染症患者の炎症反応、免疫応答や臓器障害に関する評価を行い、リキッドバイオプシー(体液による病態解析・診断)を可能とするアッセイシステムを構築する。
    小児期には急性脳炎・脳症、劇症肝炎・急性肝不全、心筋炎などの重篤な感染症が存在する。基礎疾患や免疫抑制剤の投与により易感染性を示す患者は、血流感染症などの重症感染症のリスクにさらされる。これら重症感染症では、病原微生物は幅広く、通常は複数の検査を平行して病原微生物の同定を試みる。重症感染症では、早期診断と適切な抗微生物薬の選択が予後を左右する。次世代シークエンス法は、一度のアッセイで、1,000万~10億程度のリード(DNA・RNA断片のシークエンス数)を得ることができ、臨床検体中の核酸断片を網羅的・定量的に解析できる。さらに薬剤耐性も同時に解析可能である。重症感染症における病原微生物診断は現状では不十分であり、多くの症例で診断できれば、抗微生物薬の効率的な使用が可能になり、感染症診療に大きな進展が予想される。生体内の微生物分布(マイクロバイオーム)を調べる方法は臨床診断法にそのまま応用できない。次世代シークエンス法を臨床応用できる基盤的研究を推進し、重症感染症の病原を早期に網羅的に診断できる方法を開発する。
    2019年度は、150bpの断片配列を読むショートリード法、網羅的な解析を念頭にショットガン法により、血液培養・核酸検出法に比べて、病原微生物検出における次世代シークエンスの位置づけを検討した。シークエンスデータの解析は、2019年12月にウェブ上で公開した解析パイプライン「PATHDET」(新規に開発)を使用した。発熱性好中球減少症の病原微生物確定診断例は10~20%であり、多くは原因不明である。次世代シークエンス法による病原微生物の診断は、血液培養陽性例では全例可能であり、血液培養陰性例では15%程度の症例で病原微生物が検出できた。
    2019年は主に発熱性好中球減少症の血漿検体を解析し、次世代シークエンス診断法の優位性を示唆する結果を得た。重症感染症の臨床検体中のcell-free DNAやmiRNAの分離・解析について、検討を進めている。
    発熱性好中球減少症以外の疾患のデータを蓄積する。
    次世代シークエンスを用いて、重症感染症の血液・髄液検体のcell-free DNAおよびmiRNAの分離・解析を進め、感染症の急性期に病態把握につながる結果が得られないか、引き続き検討する。重症感染症におけるリンパ球検体を用いた次世代シークエンス解析により、免疫応答を多面的に解析できないか、検討する。

  6. DNA損傷応答蛋白質の網羅的インタラクトーム解析

    Grant number:18K11639  2018.4 - 2021.3

    黒谷 賢一

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    DNA損傷応答 (DNA damage response, DDR)はゲノムの安定化に極めて重要な反応である。DDR蛋白質の細胞内での機能を理解するためには、蛋白質-蛋白質間の相互作用 (Protein-protein interaction, PPI)ネットワークを詳細に知る必要がある。本研究では、精密質量分析装置を利用した、ヒト細胞におけるDDR蛋白質の網羅的インタラクトーム解析を実施する。新規のDDR蛋白質の同定ならびにその機能解析を実施することで、DDRの理解を深めることを目的とする。
    2019年度は、インタラクトーム解析を生理的条件下で実施するために、ゲノム編集技術を利用し、標的遺伝子のC末端領域にタグ遺伝子配列と薬剤選択遺伝子配列の導入を行った。その結果、ゲノム編集後に細胞内で比較的高コピー数の蛋白質 (蛍光顕微鏡にてmCloverのシグナルで判断)を発現する遺伝子を複数見出した。 ゲノム編集により、mClover配列とともにStrep配列を挿入しており、Strep-Tactinシステムを用いて、標的蛋白質を濃縮するための条件検討を行った。しかしながら、精密質量分析装置を用いた網羅的インタラクトーム解析に十分な標的蛋白質の量を回収することができなかった。解析に必要な十分な標的蛋白質量を確保するためには、解析細胞数の増量、もしくはStrep-Tactinシステムによるプルダウン効率の上昇が必要であると考えられる。
    網羅的インタラクトーム解析を内在性蛋白質に対して実施するために、ゲノム編集技術を利用した、mClover、Strep、薬剤耐性遺伝子の導入を実施した。その結果、複数の標的遺伝子に対するゲノム編集をDNA/蛋白質レベルで確認することができた。標的遺伝子に対するゲノム編集が確認された細胞に対して、Strep-Tactinシステムを用いたプルダウン法を実施したが、精密質量分析装置を用いた網羅的インタラクトーム解析に十分な標的蛋白質量を確保することができなかった。標的遺伝子の細胞内での発現量が低い場合においても、網羅的インタラクトーム解析に必要十分な蛋白質量を確保するための条件検討を実施する必要性が出たため。
    2020年度は、ゲノム編集が確認された細胞から蛋白質を抽出し、精密質量分析装置を用いた網羅的インタラクトーム解析に十分な標的蛋白質量を確保するための条件検討を実施する。Strep-Tactinシステムを用いたプルダウン法の効率を上げるため、現状のStrep配列1個からタンデムに2個並べたコンストラクトを作製する。また、解析細胞数についても条件検討を行う。外来遺伝子を細胞へ導入し発現させた蛋白質に対しても、インタラクトーム解析の実施準備を行う。網羅的インタラクトーム解析に必要な蛋白質を安定して回収することが可能となった後に、精密質量分析のためのサンプル調整について条件検討を実施する。DDR蛋白質のインタラクトーム解析により、新規蛋白質-蛋白質間相互作用、ならびに機能未知の蛋白質との相互作用が検出された際には、分子生物学的手法を用いた解析を実施する。具体的には、標的蛋白質に対する抗体を用いた免疫沈降法により、質量分析装置で得られた実験結果の確認を行う。また、機能未知蛋白質の細胞内で役割を検討するため、siRNA法ならびにゲノム編集技術により機能喪失させた細胞を作製し、DDRへの関与の有無を検討する。

  7. プロテオーム解析によるDNA損傷応答システムの破綻により生じる疾患発症因子の同定

    Grant number:18H03372  2018.4 - 2021.3

    岡 泰由

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    DNA損傷応答 (DNA damage response, DDR)システムの破綻によって、ヒトでは様々な病態を示す遺伝性疾患を発症することが知られているが、依然として、疾患発症原因が不明なものが多く残されている。昨今の大規模ゲノム解析研究から、健常人のゲノムにも数多くの遺伝子変異が存在することが明らかにされてきた。エクソーム解析を行ったとしても、疾患原因遺伝子変異の絞り込みが困難なため、確定診断に至るのは20-30%程度といわれている。本研究の目的は、ゲノム解析結果とプロテオーム解析データを統合することで、ゲノム解析のみでは候補遺伝子を絞り込むことができなかった、DDRシステムの破綻によって発症した遺伝性疾患の発症因子を特定し、DDRシステムと多様な病態を示す遺伝性疾患との関連性を明らかにすることである。
    エクソーム解析のみでは候補遺伝子変異の絞り込みには至らなかった、DDRシステムの破綻によって発症することが知られているゼッケル症候群疑いと診断された患者由来の不死化血球系細胞について、プロテオーム解析を実施した。その結果、核酸代謝関連酵素の蛋白質発現が健常人由来細胞と比較して顕著に低下していること、当該蛋白質が細胞内で相互作用している因子の発現量が低下していることが明らかとなった。エクソーム解析では、当該遺伝子の病的変異の同定には至らなかったため、全ゲノム解析ならびにRNA-seq解析を実施した。その結果、当該遺伝子イントロン深部に疾患発症に関連することが予想される変異を同定し、その領域を含んだ異常スプライシング産物が患者細胞特異的に合成されていることを見出した。
    これまでに、エクソーム解析のみでは候補遺伝子変異の絞り込みには至らなかった、DDRシステムの破綻によって発症したことが疑われる症例について、プロテオーム解析により疾患発症の原因となり得る候補因子を絞り込み、疾患発症関連因子の蛋白質発現低下に加えて、細胞内で疾患発症関連因子と複合体を形成することで安定化している蛋白質についても発現量の低下を検出することができている。さらに、全ゲノム解析とRNA-seq解析により、当該遺伝子のイントロン深部に病的変異を見出し、異常スプライシング産物が患者細胞において合成されていることを明らかとしたため。
    プロテオーム解析により絞り込みに成功した症例については、患者細胞において、核酸代謝酵素機能低下の有無を、分子生物学的実験手法を用いて明らかにする。エクソーム解析のみでは候補遺伝子変異の絞り込みには至らなかった、DDRシステムの破綻によって発症したことが疑われる症例について、引き続きプロテオーム解析を実施する。DDRシステムの破綻によって発症したことが疑われる症例の追加収集を行う。

  8. 中部東海地区IRUDゲノム解析拠点-先端情報技術の融合による包括的遺伝子診断の提供

    2018.3 - 2021.3

    科学研究費補助金  その他

  9. DNA修復・損傷応答機構の異常により発症するゲノム不安定性疾患の分子病態解明研究

    2017.4 - 2020.3

    科学研究費補助金  基盤研究(A)

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  10. ゲノム不安定性疾患群を中心とした希少難治性疾患の次世代マルチオミクス診断拠点構築

    2017.4 - 2020.3

    科学研究費補助金  その他

  11. DNA修復・損傷応答機構の異常により発症するゲノム不安定性疾患の分子病態解明研究

    2017.4 - 2020.3

    科学研究費補助金  その他

  12. DNA double strand break repair factors mutated in a new syndrome with microcephaly

    Grant number:17H01877  2017.4 - 2020.3

    NAKAZAWA Yuka

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    In this study, we have focused on microcephaly as a commonly observed clinical feature of DNA repair deficiency disorders. We have identified several new pathogenic variants in DNA repair genes from microcephaly cases and tried to elucidate their molecular pathogenesis. We have generated mice with mutations in those newly determined genes; however, we often experienced lack of expected phenotypes. This is partly due to greater tolerance to DNA damages in mice; we decided to cross the animals with other mice with deficiency in different DNA repair processes so that overload DNA damage to elicit a phenotype. From this approach, we found that microcephaly and some types of neurodegeneration diseases can be explained by prolonged arrest of RNA polymerases at DNA damage sites during transcription. DNA damage stalled RNA polymerases are ubiquitinated to facilitate DNA repair; when this process is compromised, various neurodegenerative phenotypes, as shown in Cockayne syndrome, come up.

  13. Molecular pathogenesis of human genetic disorders associated with deficiency in the DNA repair and damage response system

    Grant number:17H00783  2017.4 - 2020.3

    OGI Tomoo

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    Authorship:Principal investigator 

    Grant amount:\42770000 ( Direct Cost: \32900000 、 Indirect Cost:\9870000 )

    We have investigated on human genetic disorders associated with genome instability. Patients with these syndromes have developed various clinical manifestations due to malfunctions of DNA repair and damage response system. We have collected undiagnosed cases and tried to elucidate the genetic cause of diseases using the Multi-omics approach that involves next-generation sequencing, high-accurate mass spectrometry, and precise DNA repair assays. Once we identified pathogenic variants, we have performed in vitro and in vivo analyses as well as animal studies so that we could get new insights into the molecular pathogenesis of the diseases. Recently, we have reported a detailed molecular mechanism of the initiation of transcription-coupled repair, which is compromised in Cockayne syndrome.

  14. Genetic diagnosis of microcephaly

    Grant number:16K15526  2016.4 - 2018.3

    OGI Tomoo

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    Authorship:Principal investigator 

    Grant amount:\3510000 ( Direct Cost: \2700000 、 Indirect Cost:\810000 )

    Primary microcephaly is partially caused by deficiencies in DNA Damage Response system (DDR system). As prevalence of these genetic disorders are very rare and the patients usually display overlapping clinical features, we often face with difficulties in the clinical diagnosis.
    In this project, we aimed to develop a system helpful in the differential diagnosis of microcephaly and similar conditions. The developed system comprises next generation DNA sequencing (NGS) as well as DDR activity assays for detecting deficiencies in double strand break (DSB) repair and nucleotide excision repair (NER).

  15. 小頭症を発症する遺伝性疾患の鑑別診断技術開発

    2016.4 - 2017.3

    科学研究費補助金  研究成果公開促進費 (研究成果公開発表)

    荻 朋男

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  16. 小頭症を発症する遺伝性疾患の鑑別診断技術開発

    2016.4 - 2017.3

    科学研究費助成事業  挑戦的研究(萌芽)

    荻 朋男

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\2080000 ( Direct Cost: \1600000 、 Indirect Cost:\480000 )

  17. Molecular regions of BRCA proteins responsible for cancer suppression

    Grant number:15K06833  2015.4 - 2019.3

    Takenaka Katsuya

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    BRCA2 germline mutations account for the majority of heredity breast and ovarian cancer. A major function of BRCA2 is known as a regulator of homologous recombination in DNA damage repair. In addition, BRCA2 also plays an important role in centrosomal regulation, whose dysfunction might be involved inthe tumorigenesis of breast cancer. Though, detail molecular mechanism was not uncovered. In the present study, we tried to locate a molecular region of BRCA2 responsible for this function. Numbers of centrosome in a cell are counted to see if an overexpression of a specific fragment of BRCA proteins could impair a numerical integrity of centrosomes. For this purpose we developed an automated centrosome-counting system based on image recognition, which allows us to judge a large number of transfected cells without human bias.

  18. ゲノム不安定性を誘発する先天性稀少疾患と小児がんコホートの分子遺伝疫学調査

    2015.4 - 2018.3

    科学研究費補助金  基盤研究(A)

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    Authorship:Principal investigator 

  19. ゲノム不安定性を誘発する先天性稀少疾患と小児がんコホートの分子遺伝疫学調査

    2015.4 - 2018.3

    科学研究費補助金  その他

  20. Molecular epidemiology studies on rare genetic disorders and pediatric cancer cohorts associated with genome instability

    Grant number:15H02654  2015.4 - 2018.3

    OGI Tomoo

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    Authorship:Principal investigator 

    Grant amount:\42900000 ( Direct Cost: \33000000 、 Indirect Cost:\9900000 )

    Genomic DNA is constitutively exposed to various DNA damaging sources; therefore, the DNA repair and damage response system is essential for the maintenance and stable transmission of the genetic information. A failure in this system elicits genome instability and causes carcinogenesis and ageing. In this study, we have collected various hereditary disorder cases world-widely to identify genetic factors associated with congenital genome instability. We generated a pathogenic mutation database as well as a cell-bank from the analysis of collected samples. We have identified several new DNA repair genes with novel pathogenic mutations. We are currently working on the molecular pathogenesis of newly identified mutations and their associated genetic disorders.

  21. Biochemical analysis of transcription coupled nucleotide excision repair factors

    Grant number:15K00541  2015.4 - 2018.3

    KARATA Kiyonobu

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    The detailed function of TC-NER-specific factors, CSA, CSB and UVSSA, remains to be defined. In order to elucidate their function biochemically, we tried to reconstitute in vitro TC-NER assay system using DNA templates harboring a site-directed DNA damage. In addition, we have developed the purification method of UVSSA protein for its X-ray crystal structure analysis.

  22. The molecular epidemiological study of DNA repair-related genes in post-Chernobyl radiation-induced thyroid cancers

    Grant number:26293142  2014.4 - 2019.3

    MITSUTAKE Norisato

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    Mutation data were obtained by next-generation sequencing using genomic DNA of 56 post-Chernobyl radiation-induced pediatric thyroid cancer cases and 55 controls who were also lived in the same area and exposed but without development of thyroid cancer. Although several candidate genes related to carcinogenesis were found, further research is needed. No obvious accumulation of mutations was identified among DNA repair genes. Through this project, we were able to acquire comprehensive genomic data of the invaluable samples and established the basis of continuous research in future.

  23. 転写共役ヌクレオチド除去修復開始反応のin vitro再構成

    2014.4 - 2018.3

    科学研究費補助金  基盤研究(B)

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  24. 転写共役ヌクレオチド除去修復開始反応のin vitro再構成

    2014.4 - 2018.3

    科学研究費補助金  その他

  25. In vitro reconstitution of the initiation process of transcription-coupled nucleotide-excision repair

    Grant number:26291005  2014.4 - 2018.3

    OGI Tomoo

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    Authorship:Principal investigator 

    Grant amount:\16640000 ( Direct Cost: \12800000 、 Indirect Cost:\3840000 )

    Transcription-coupled nucleotide-excision repair (TC-NER) is one of the versatile DNA repair process that removes major UV-induced DNA lesions from actively transcribed genes. To investigate the initiation process of TC-NER reaction, we focused on a molecular mechanism that involves DNA-damage induced ubiquitination of RNA polymerase IIo (RNA pol IIo). The process is dependent on a recently identified TC-NER factor, UVSSA.
    To determine the ubiquitination sites, we performed in vitro ubiquitination assay as well as SILAC-based High-Resolution Accurate Mass (HRAM) spectrometry. From the studies, we identified UVSSA-dependent ubiquitination sites required for the efficient TC-NER activity.

  26. Mechanism of genomic DNA damage response mediated by acetylation of non-histone proteins

    Grant number:26281026  2014.4 - 2018.3

    YASUDA Takeshi

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    We newly identified several non-histone proteins involved in DNA damage response, which are acetylated by p300 and CBP histone acetyltransferases in vitro. Among the identified acetylated proteins, we showed that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DNA double strand break (DSB) sites. We identified 13 acetylation sites in RAD52. We revealed that non-acetylated RAD52 initially accumulates at DSB sites, but dissociates prematurely from them. In the absence of RAD52 acetylation, RAD51, which plays a central role in HR, also dissociates prematurely from DSB sites, and hence HR is impaired. Furthermore, we demonstrated that the acetylation of RAD52 is linked to ATM signaling. Our findings clarify the importance of RAD52 acetylation in HR.

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    Grant type:Competitive

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    Grant type:Competitive

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