Updated on 2022/08/05

写真a

 
MASUTANI, Chikahide
 
Organization
Research Institute of Environmental Medicine Division of Stress Adaptation and Protection Professor
Graduate School
Graduate School of Medicine
Title
Professor

Degree 1

  1. Ph.D. ( 1991.3   The University of Tokyo ) 

Research History 10

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

    2010.9

  2. 名古屋大学環境医学研究所 教授

    2010.9

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    Country:Japan

  3. 大阪大学大学院生命機能研究科 准教授

    2007.4 - 2010.8

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    Country:Japan

  4. Osaka University   Graduate School of Frontier Biosciences

    2007.4 - 2010.8

  5. 大阪大学大学院生命機能研究科 助教授

    2005.7 - 2007.3

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    Country:Japan

  6. ピッツバーグ大学癌研究所 日米がん派遣研究者

    2003.6 - 2003.8

  7. 大阪大学大学院生命機能研究科 助手

    2002.4 - 2005.6

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    Country:Japan

  8. 大阪大学細胞生体工学センター 助手

    1995.4 - 2002.3

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    Country:Japan

  9. 理化学研究所 研究員

    1994.4 - 1995.3

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    Country:Japan

  10. 理化学研究所 基礎科学特別研究員

    1991.4 - 1994.3

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    Country:Japan

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Education 2

  1. The University of Tokyo   Graduate School, Division of Pharmaceutical Sciences

    1986.4 - 1991.3

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    Country: Japan

  2. The University of Tokyo   Faculty of Pharmaceutical Science

    1982.4 - 1986.3

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    Country: Japan

 

Papers 124

  1. RFWD3 and translesion DNA polymerases contribute to PCNA modification-dependent DNA damage tolerance Reviewed

    Rie Kanao, Hidehiko Kawai, Toshiyasu Taniguchi, Minoru Takata, Chikahide Masutani

    Life Science Alliance   Vol. 5 ( 12 )   2022.7

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.26508/lsa.202201584

  2. Regulation of HLTF-mediated PCNA polyubiquitination by RFC and PCNA monoubiquitination levels determines choice of damage tolerance pathway. Reviewed

    Masuda Y, Mitsuyuki S, Kanao R, Hishiki A, Hashimoto H, Masutani C

    Nucleic acids research     2018.10

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    Authorship:Last author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/nar/gky943

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  3. USP7 is a suppressor of PCNA ubiquitination and oxidative-stress-induced mutagenesis in human cells. Reviewed

    Kashiwaba, S., Kanao, R., Masuda, Y., Kusumoto-Matsuo, R., Hanaoka, F., Masutani, C.

    Cell Reports   Vol. 13   page: 2072-2080   2015.12

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j. celrep.2015.11.014

  4. Different types of interaction between PCNA and PIP boxes contribute to distinct cellular functions of Y-family DNA polymerases Reviewed

    Masuda Yuji, Kanao Rie, Kaji Kentaro, Ohmori Haruo, Hanaoka Fumio, Masutani Chikahide

    NUCLEIC ACIDS RESEARCH   Vol. 43 ( 16 ) page: 7898 - 7910   2015.9

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/nar/gkv712

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  5. Relevance of simultaneous mono-ubiquitinations of multiple units of PCNA homo-trimers in DNA damage tolerance. Reviewed International journal

    Rie Kanao, Yuji Masuda, Saori Deguchi, Mayumi Yumoto-Sugimoto, Fumio Hanaoka, Chikahide Masutani

    PloS one   Vol. 10 ( 2 ) page: e0118775   2015.2

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    Authorship:Last author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)  

    DNA damage tolerance (DDT) pathways, including translesion synthesis (TLS) and additional unknown mechanisms, enable recovery from replication arrest at DNA lesions. DDT pathways are regulated by post-translational modifications of proliferating cell nuclear antigen (PCNA) at its K164 residue. In particular, mono-ubiquitination by the ubiquitin ligase RAD18 is crucial for Polη-mediated TLS. Although the importance of modifications of PCNA to DDT pathways is well known, the relevance of its homo-trimer form, in which three K164 residues are present in a single ring, remains to be elucidated. Here, we show that multiple units of a PCNA homo-trimer are simultaneously mono-ubiquitinated in vitro and in vivo. RAD18 catalyzed sequential mono-ubiquitinations of multiple units of a PCNA homo-trimer in a reconstituted system. Exogenous PCNA formed hetero-trimers with endogenous PCNA in WI38VA13 cell transformants. When K164R-mutated PCNA was expressed in these cells at levels that depleted endogenous PCNA homo-trimers, multiple modifications of PCNA complexes were reduced and the cells showed defects in DDT after UV irradiation. Notably, ectopic expression of mutant PCNA increased the UV sensitivities of Polη-proficient, Polη-deficient, and REV1-depleted cells, suggesting the disruption of a DDT pathway distinct from the Polη- and REV1-mediated pathways. These results suggest that simultaneous modifications of multiple units of a PCNA homo-trimer are required for a certain DDT pathway in human cells.

    DOI: 10.1371/journal.pone.0118775

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  6. Mechanisms of accurate translesion synthesis by human DNA polymerase h. Reviewed

    Masutani, C., Kusumoto, R., Iwai, S., and Hanaoka, F.

    EMBO J.   Vol. 19   page: 3100-3109   2000

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  7. Xeroderma pigmentosum variant (XP-V) correcting protein from HeLa cells has a thymine dimer bypass DNA polymerase activity. Reviewed

    Masutani, C., Araki, M., Yamada, A., Kusumoto, R., Nogimori, T., Maekawa, T., Iwai, S., and Hanaoka, F.

    EMBO J.   Vol. 18   page: 3491-3501   1999

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  8. The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase h. Reviewed

    Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., and Hanaoka, F.

    Nature   Vol. 399   page: 700-704   1999

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  9. Acetaldehyde induces NER repairable mutagenic DNA lesions. Reviewed

    Sonohara Y, Takatsuka R, Masutani C, Iwai S, Kuraoka I

    Carcinogenesis     2021.9

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    DOI: 10.1093/carcin/bgab087

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  10. Stepwise multipolyubiquitination of p53 by the E6AP-E6 ubiquitin ligase complex Reviewed

    Masuda Yuji, Saeki Yasushi, Arai Naoko, Kawai Hidehiko, Kukimoto Iwao, Tanaka Keiji, Masutani Chikahide

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 294 ( 41 ) page: 14860 - 14875   2019.10

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    DOI: 10.1074/jbc.RA119.008374

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  11. Spatiotemporal regulation of PCNA ubiquitination in damage tolerance pathways Reviewed

    Masuda Yuji, Masutani Chikahide

    CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY   Vol. 54 ( 5 ) page: 418 - 442   2019.9

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    Authorship:Last author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1080/10409238.2019.1687420

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  12. Preferential digestion of PCNA-ubiquitin and p53-ubiquitin linkages by USP7 to remove polyubiquitin chains from substrates. Reviewed

    Masuda Y, Kanao R, Kawai H, Kukimoto I, Masutani C

    The Journal of biological chemistry     2019.1

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    DOI: 10.1074/jbc.RA118.005167

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  13. Regulation of DNA damage tolerance in mammalian cells by post-translational modifications of PCNA Reviewed

    Kanao Rie, Masutani Chikahide

    MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS   Vol. 803   page: 82 - 88   2017.10

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    DOI: 10.1016/j.mrfmmm.2017.06.004

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  14. Biochemical analysis of HLTF, a human homologue of SWI/SNF-related ubiquitin ligase RAD5

    Masuda Yuji, Kanao Rie, Masutani Chikahide

    GENES & GENETIC SYSTEMS   Vol. 91 ( 6 ) page: 366 - 366   2016.12

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  15. Stimulation of human DNA polymerase eta by PCNA

    Masuda Yuji, Kanao Rie, Masutani Chikahide

    GENES & GENETIC SYSTEMS   Vol. 90 ( 6 ) page: 368 - 368   2015.12

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  16. The BAH domain of BAF180 is required for PCNA ubiquitination. Reviewed

    Niimi A, Hopkins SR, Downs JA, Masutani C

    Mutation Research   Vol. 779   page: 16-23   2015.6

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    DOI: 10.1016/j.mrfmmm.2015.06.006.

  17. UV-induced mutations in epidermal cells of mice defective in DNA polymerase η and/or ι. Reviewed

    Kanao R., Yokoi M., Ohkumo T., Sakurai Y., Dotsu K., Kura S., Nakatsu Y., Tsuzuki T., Masutani C., Hanaoka F.

    DNA Repair (Amst)   Vol. 29   page: 139-146   2015.5

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    DOI: 10.1016/j.dnarep.2015.02.006.

  18. UV-induced mutations in epidermal cells of mice defective in DNA polymerase eta and/or iota

    Kanao Rie, Yokoi Masayuki, Ohkumo Tsuyoshi, Sakurai Yasutaka, Dotsu Kantaro, Kura Shinobu, Nakatsu Yoshimichi, Tsuzuki Teruhisa, Masutani Chikahide, Hanaoka Fumio

    DNA REPAIR   Vol. 29   page: 139 - 146   2015.5

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:DNA Repair  

    Xeroderma pigmentosum variant (XP-V) is a human rare inherited recessive disease, predisposed to sunlight-induced skin cancer, which is caused by deficiency in DNA polymerase η (Polη). Polη catalyzes accurate translesion synthesis (TLS) past pyrimidine dimers, the most prominent UV-induced lesions. DNA polymerase ι (Polι) is a paralog of Polη that has been suggested to participate in TLS past UV-induced lesions, but its function in vivo remains uncertain. We have previously reported that Polη-deficient and Polη/Polι double-deficient mice showed increased susceptibility to UV-induced carcinogenesis. Here, we investigated UV-induced mutation frequencies and spectra in the epidermal cells of Polη- and/or Polι-deficient mice. While Polη-deficient mice showed significantly higher UV-induced mutation frequencies than wild-type mice, Polι deficiency did not influence the frequencies in the presence of Polη. Interestingly, the frequencies in Polη/Polι double-deficient mice were statistically lower than those in Polη-deficient mice, although they were still higher than those of wild-type mice. Sequence analysis revealed that most of the UV-induced mutations in Polη-deficient and Polη/Polι double-deficient mice were base substitutions at dipyrimidine sites. An increase in UV-induced mutations at both G:C and A:T pairs associated with Polη deficiency suggests that Polη contributes to accurate TLS past both thymine- and cytosine-containing dimers in vivo. A significant decrease in G:C to A:T transition in Polη/Polι double-deficient mice when compared with Polη-deficient mice suggests that Polι is involved in error-prone TLS past cytosine-containing dimers when Polη is inactivated.

    DOI: 10.1016/j.dnarep.2015.02.006

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  19. Relevance of simultaneous mono-ubiquitnations of multiple units of PCNA homo-trimers in DNA damage tolerance. Reviewed

    Kanao R, Masuda Y, Deguchi S, Yumoto-Sugimoto M, Hanaoka F, Masutani C

    PLoS One   Vol. 10 ( 2 ) page: e0118775   2015.2

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    DOI: doi: 10.1371/journal.pone.0118775

  20. P-002 Interaction between PCNA and human DNA polymerase eta(Poster Sessions)

    Masuda Yuji, Kanao Rie, Masutani Chikahide

      ( 44 )   2015

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  21. Analysis of PCNA interacting motifs of DNA polymerase

    Masuda Yuji, Kanao Rie, Ohmori Haruo, Hanaoka Fumio, Masutani Chikahide

    GENES & GENETIC SYSTEMS   Vol. 89 ( 6 ) page: 309 - 309   2014.12

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  22. Sphingosine, a Modulator of Human Translesion DNA Polymerase Activity

    Kamath-Loeb Ashwini S., Balakrishna Sharath, Whittington Dale, Shen Jiang-Cheng, Emond Mary J., Okabe Takayoshi, Masutani Chikahide, Hanaoka Fumio, Nishimura Susumu, Loeb Lawrence A.

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 289 ( 31 ) page: 21663 - 21672   2014.8

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Journal of Biological Chemistry  

    Translesion (TLS) DNA polymerases are specialized, error-prone enzymes that synthesize DNA across bulky, replication-stalling DNA adducts. In so doing, they facilitate the progression of DNA synthesis and promote cell proliferation. To potentiate the effect of cancer chemotherapeutic regimens, we sought to identify inhibitors of TLS DNA polymerases. We screened five libraries of ∼3000 small molecules, including one comprising ∼600 nucleoside analogs, for their effect on primer extension activity of DNA polymerase η (Polη). We serendipitously identified sphingosine, a lipid-signaling molecule that robustly stimulates the activity of Pol η by ∼100-fold at low micromolar concentrations but inhibits it at higher concentrations. This effect is specific to the Y-family DNA polymerases, Pols η, κ, and ι. The addition of a single phosphate group on sphingosine completely abrogates this effect. Likewise, the inclusion of other sphingolipids, including ceramide and sphingomyelin to extension reactions does not elicit this response. Sphingosine increases the rate of correct and incorrect nucleotide incorporation while having no effect on polymerase processivity. Endogenous Pol η activity is modulated similarly as the recombinant enzyme. Importantly, sphingosine-treated cells exhibit increased lesion bypass activity, and sphingosine tethered to membrane lipids mimics the effects of free sphingosine. Our studies have uncovered sphingosine as a modulator of TLS DNA polymerase activity; this property of sphingosine may be associated with its known role as a signaling molecule in regulating cell proliferation in response to cellular stress. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

    DOI: 10.1074/jbc.M114.570242

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  23. Sphingosine: A Modulator of Human Translesion DNA Polymerase Activity. Reviewed

    Kamath-Loeb AS, Balakrishna S, Whittington D, Shen JC, Emond MJ, Okabe T, Masutani C, Hanaoka F, Nishimura S, Loeb LA.

    Journal of Biological Chemistry     2014.7

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    DOI: jbc.M114.570242.

  24. Guanine- 5-carboxylcytosine base pairs mimic mismatches during DNA replication. Reviewed International journal

    Toshihiro Shibutani, Shinsuke Ito, Mariko Toda, Rie Kanao, Leonard B Collins, Marika Shibata, Miho Urabe, Haruhiko Koseki, Yuji Masuda, James A Swenberg, Chikahide Masutani, Fumio Hanaoka, Shigenori Iwai, Isao Kuraoka

    Scientific reports   Vol. 4   page: 5220 - 5220   2014.6

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    The genetic information encoded in genomes must be faithfully replicated and transmitted to daughter cells. The recent discovery of consecutive DNA conversions by TET family proteins of 5-methylcytosine into 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine (5caC) suggests these modified cytosines act as DNA lesions, which could threaten genome integrity. Here, we have shown that although 5caC pairs with guanine during DNA replication in vitro, G·5caC pairs stimulated DNA polymerase exonuclease activity and were recognized by the mismatch repair (MMR) proteins. Knockdown of thymine DNA glycosylase increased 5caC in genome, affected cell proliferation via MMR, indicating MMR is a novel reader for 5caC. These results suggest the epigenetic modification products of 5caC behave as DNA lesions.

    DOI: 10.1038/srep05220

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  25. A cyclobutane thymine-N4-methylcytosine dimer is resistant to hydrolysis but strongly blocks DNA synthesis. Reviewed International journal

    Junpei Yamamoto, Tomoko Oyama, Tomohiro Kunishi, Chikahide Masutani, Fumio Hanaoka, Shigenori Iwai

    Nucleic acids research   Vol. 42 ( 3 ) page: 2075 - 2084   2014.2

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    Exposure of DNA to ultraviolet light produces harmful crosslinks between adjacent pyrimidine bases, to form cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts. The CPD is frequently formed, and its repair mechanisms have been exclusively studied by using a CPD formed at a TT site. On the other hand, biochemical analyses using CPDs formed within cytosine-containing sequence contexts are practically difficult, because saturated cytosine easily undergoes hydrolytic deamination. Here, we found that N-alkylation of the exocyclic amino group of 2'-deoxycytidine prevents hydrolysis in CPD formation, and an N-methylated cytosine-containing CPD was stable enough to be derivatized into its phosphoramidite building block and incorporated into oligonucleotides. Kinetic studies of the CPD-containing oligonucleotide indicated that its lifetime under physiological conditions is relatively long (∼ 7 days). In biochemical analyses using human DNA polymerase η, incorporation of TMP opposite the N-methylcytosine moiety of the CPD was clearly detected, in addition to dGMP incorporation, and the incorrect TMP incorporation blocked DNA synthesis. The thermodynamic parameters confirmed the formation of this unusual base pair.

    DOI: 10.1093/nar/gkt1039

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  26. Interactions between PCNA and DNA polymerases of Y-family

    Masuda Yuji, Kanao Rie, Masutani Chikahide

    GENES & GENETIC SYSTEMS   Vol. 88 ( 6 ) page: 360 - 360   2013.12

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  27. Novel mechanisms of PCNA ubiquitination

    Masuda Yuji, Masutani Chikahide

    GENES & GENETIC SYSTEMS   Vol. 87 ( 6 ) page: 387 - 387   2012.12

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  28. En bloc transfer of poly-ubiquitin chains to PCNA in vitro is mediated by two human E2-E3 pairs. Reviewed

    *Masuda, Y., Suzuki, M., Kawai, H., Hishiki, A., Hashimoto, H., Masutani, C., Hishida, T., Suzuki, F., *Kamiya. K.

    Nucl. Acids Res.   Vol. 40 ( 20 ) page: 10394-10407   2012.11

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  29. En bloc transfer of polyubiquitin chains to PCNA in vitro is mediated by two different human E2-E3 pairs

    Masuda Yuji, Suzuki Miki, Kawai Hidehiko, Hishiki Asami, Hashimoto Hiroshi, Masutani Chikahide, Hishida Takashi, Suzuki Fumio, Kamiya Kenji

    NUCLEIC ACIDS RESEARCH   Vol. 40 ( 20 ) page: 10394 - 10407   2012.11

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    Post-replication DNA repair in eukaryotes is regulated by ubiquitination of proliferating cell nuclear antigen (PCNA). Monoubiquitination catalyzed by RAD6-RAD18 (an E2-E3 complex) stimulates translesion DNA synthesis, whereas polyubiquitination, promoted by additional factors such as MMS2-UBC13 (a UEV-E2 complex) and HLTF (an E3 ligase), leads to template switching in humans. Here, using an in vitro ubiquitination reaction system reconstituted with purified human proteins, we demonstrated that PCNA is polyubiquitinated predominantly via en bloc transfer of a pre-formed ubiquitin (Ub) chain rather than by extension of the Ub chain on monoubiquitinated PCNA. Our results support a model in which HLTF forms a thiol-linked Ub chain on UBC13 (UBC13∼Ubn) and then transfers the chain to RAD6∼Ub, forming RAD6∼Ubn+1. The resultant Ub chain is subsequently transferred to PCNA by RAD18. Thus, template switching may be promoted under certain circumstances in which both RAD18 and HLTF are coordinately recruited to sites of stalled replication. © 2012 The Author(s).

    DOI: 10.1093/nar/gks763

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  30. Human DNA Polymerase η and Its Regulatory Mechanisms

    Masutani Chikahide

    Genes and environment : the official journal of the Japanese Environmental Mutagen Society   Vol. 34 ( 2 ) page: 63 - 69   2012.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:日本環境変異原学会  

    Defects in DNA polymerase (Pol) &eta; result in a cancer-prone and UV-sensitive inherited syndrome, a variant form of xeroderma pigmentosum, suggesting that Pol&eta; plays a vital role in preventing UV-induced skin cancers. In fact, Pol&eta; can catalyze translesion synthesis (TLS) past prominent UV-induced lesions efficiently and accurately. However, Pol&eta; is intrinsically an error-prone DNA polymerase, like other TLS polymerases. Biochemical, structural and physiological studies revealed that Pol&eta; and other TLS polymerases participate in multiple mutagenic mechanisms, including somatic hypermutation of immunoglobulin genes. Protein-protein interactions between Pol&eta; and PCNA, TLS polymerases, RAD18 and DNA repair proteins, as well as their posttranslational modifications, have been shown to be important for regulating Pol&eta;.<br>

    DOI: 10.3123/jemsge.34.63

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  31. NBS1 Recruits RAD18 via a RAD6-like Domain and Regulates Pol eta-Dependent Translesion DNA Synthesis

    Yanagihara Hiromi, Kobayashi Junya, Tateishi Satoshi, Kato Akihiro, Matsuura Shinya, Tauchi Hiroshi, Yamada Kouichi, Takezawa Jun, Sugasawa Kaoru, Masutani Chikahide, Hanaoka Fumio, Weemaes Corry M., Mori Toshio, Zou Lee, Komatsu Kenshi

    MOLECULAR CELL   Vol. 43 ( 5 ) page: 788 - 797   2011.9

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    Translesion DNA synthesis, a process orchestrated by monoubiquitinated PCNA, is critical for DNA damage tolerance. While the ubiquitin-conjugating enzyme RAD6 and ubiquitin ligase RAD18 are known to monoubiquitinate PCNA, how they are regulated by DNA damage is not fully understood. We show that NBS1 (mutated in Nijmegen breakage syndrome) binds to RAD18 after UV irradiation and mediates the recruitment of RAD18 to sites of DNA damage. Disruption of NBS1 abolished RAD18-dependent PCNA ubiquitination and Polη focus formation, leading to elevated UV sensitivity and mutation. Unexpectedly, the RAD18-interacting domain of NBS1, which was mapped to its C terminus, shares structural and functional similarity with the RAD18-interacting domain of RAD6. These domains of NBS1 and RAD6 allow the two proteins to interact with RAD18 homodimers simultaneously and are crucial for Polη-dependent UV tolerance. Thus, in addition to chromosomal break repair, NBS1 plays a key role in translesion DNA synthesis. © 2011 Elsevier Inc.

    DOI: 10.1016/j.molcel.2011.07.026

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  32. NBS1 recruits RAD18 via a RAD6-like domain and regulates Polh-dependent translesion DNA synthesis. Reviewed

    Yanagihara, H., Kobayashi, J., Tateishi, S., Kato, A., Matsuura, S., Tauchi, H., Yamada, K., Takwzawa, J., Sugasawa, K., Masutani, C., Hanaoka, F., Weemaes, C.M., Mori, T., Zou, L., Komatsu. K.

    Mol. Cell   Vol. 43 ( 5 ) page: 788-797   2011.9

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  33. Molecular chaperone Hsp90 regulates REV1-mediated mutagenesis Reviewed

    Pozo, F.M., Oda, T., sekimoto, T., Murakumo, Y., Masutani, C., Hanaoka, F., Yamashita, T.

    Mol. Cell. Biol.   Vol. 31 ( 16 ) page: 3396-3409   2011.8

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  34. Photosensitized [2+2] cycloaddition of N-acetylated cytosine affords stereoselective formation of cyclobutane pyrimidine dimer. Reviewed

    Yamamoto, J., nishiguchi, K., Manabe, K., Masutani, C., Hanaoka, F., Iwai, S.

    Nucl. Acids Res.   Vol. 39   page: 1165-1175   2011.2

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  35. Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions.

    Hirota K, Sonoda E, Kawamoto T, Motegi A, Masutani C, Hanaoka F, Szüts D, Iwai S, Sale JE, Lehmann A, Takeda S

    PLoS genetics   Vol. 6 ( 10 )   2010.10

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    DOI: 10.1371/journal.pgen.1001151

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  36. Simultaneous disruption of two DNA polymerases, Polh and Polz, in Avian DT40 cells unmasks the role of Polh in cellular response to various DNA lesions. Reviewed

    Hirota, K., Sonoda, E., Kawamoto, T., Motegi, A., Masutani, C., Hanaoka, F., Szuts, D., Iwai, S., Sale, J.E., Lehmann, A., Takeda, S.

    PLoS Genet.   Vol. 6 ( 10 )   2010.10

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    DOI: pii: e1001151

  37. Characterization of a Y-Family DNA Polymerase eta from the Eukaryotic Thermophile Alvinella pompejana.

    Kashiwagi S, Kuraoka I, Fujiwara Y, Hitomi K, Cheng QJ, Fuss JO, Shin DS, Masutani C, Tainer JA, Hanaoka F, Iwai S

    Journal of nucleic acids   Vol. 2010   2010.9

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    DOI: 10.4061/2010/701472

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  38. Characterization of a Y-family DNA polymerase h from the eukaryotic thermophile Alvinella pompejana. Reviewed

    Kashiwagi, S., kuraoka, I., fujiwara, Y., Hitomi, K., Cheng, Q.J., Fuss, J.O., Shin, D.S., Masutani, C., Tainer, J.A., Hanaoka, F., Iwai, S.

    J. Nucl. Acids   Vol. 2010   2010.9

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    DOI: pii: 701472

  39. Structure and mechanism of human DNA polymerase eta.

    Biertümpfel C, Zhao Y, Kondo Y, Ramón-Maiques S, Gregory M, Lee JY, Masutani C, Lehmann AR, Hanaoka F, Yang W

    Nature   Vol. 465 ( 7301 ) page: 1044 - 8   2010.6

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    DOI: 10.1038/nature09196

    PubMed

  40. Structure and mechanism of human DNA polymerase h. Reviewed

    Biertümpfel, C., Zhao, Y., Kondo, Y., Ramón-Maiques, S., Gregory, M., Lee, J.Y., Masutani, C., Lehmann, A. R., *Hanaoka, F., and *Yang, W.

    Nature   Vol. 465   page: 1044-1048   2010.6

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  41. Polymerization by DNA polymerase h is blocked by cis-diamminedichloroplatinum(II) 1,3-d(GpTpG) crosslink: Implications for cytotoxic effects in nucleotide excision repair-negative tumor cells. Reviewed

    Chijiwa, S., Masutani, C., Hanaoka, F., Iwai, S., and *Kuraoka, I.

    Carcinogenesis   Vol. 31   page: 388-393   2010.3

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  42. Polymerization by DNA polymerase eta is blocked by cis-diamminedichloroplatinum(II) 1,3-d(GpTpG) cross-link: implications for cytotoxic effects in nucleotide excision repair-negative tumor cells.

    Chijiwa S, Masutani C, Hanaoka F, Iwai S, Kuraoka I

    Carcinogenesis   Vol. 31 ( 3 ) page: 388 - 93   2010.3

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    DOI: 10.1093/carcin/bgp316

    PubMed

  43. The Molecular Chaperone Hsp90 Regulates Accumulation of DNA Polymerase eta at Replication Stalling Sites in UV-Irradiated Cells

    Sekimoto Takayuki, Oda Tsukasa, Pozo Franklin Mayca, Murakumo Yoshiki, Masutani Chikahide, Hanaoka Fumio, Yamashita Takayuki

    MOLECULAR CELL   Vol. 37 ( 1 ) page: 79 - 89   2010.1

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Molecular Cell  

    DNA polymerase η (Pol η) is a member of the mammalian Y family polymerases and performs error-free translesion synthesis across UV-damaged DNA. For this function, Pol η accumulates in nuclear foci at replication stalling sites via its interaction with monoubiquitinated PCNA. However, little is known about the posttranslational control mechanisms of Pol η, which regulate its accumulation in replication foci. Here, we report that the molecular chaperone Hsp90 promotes UV irradiation-induced nuclear focus formation of Pol η through control of its stability and binding to monoubiquitinated PCNA. Our data indicate that Hsp90 facilitates the folding of Pol η into an active form in which PCNA- and ubiquitin-binding regions are functional. Furthermore, Hsp90 inhibition potentiates UV-induced cytotoxicity and mutagenesis in a Pol η-dependent manner. Our studies identify Hsp90 as an essential regulator of Pol η-mediated translesion synthesis. © 2010 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.molcel.2009.12.015

    Web of Science

    Scopus

    PubMed

  44. Critical amino acids involved in erroneous incorporation of oxidized nucleotides by human DNA polymerase h and k. Reviewed

    Katafuchi, A., Sassa, A., Niimi, N., Gruz, P., Fujimoto, H., Masutani, C., Hanaoka, F., Ohta, T., and *Nohmi, T.

    Nucl. Acids Res.   Vol. 38   page: 859-867   2010.1

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  45. The molecular chaperone Hsp90 regulates accumulation of DNA polymerase h at replication stalling sites in UV-irradiated cells. Reviewed

    Sekimoto, T., Oda, T., Pozo, F. M., Murakumo, Y., Masutani, C., Hanaoka, F., and *Yamashita, T.

    Mol. Cell   Vol. 37   page: 79-89   2010.1

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  46. Critical amino acids in human DNA polymerases eta and kappa involved in erroneous incorporation of oxidized nucleotides.

    Katafuchi A, Sassa A, Niimi N, Grúz P, Fujimoto H, Masutani C, Hanaoka F, Ohta T, Nohmi T

    Nucleic acids research   Vol. 38 ( 3 ) page: 859 - 67   2010.1

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    DOI: 10.1093/nar/gkp1095

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  47. A novel interaction between human DNA polymerase h and MutLa. Reviewed

    Kanao, R., Hanaoka, F., and *Masutani, C.

    Biochem. Biophys. Res. Commun.   Vol. 389   page: 40-45   2009.11

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  48. Translesional DNA synthesis through a C8-guanyl adduct of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in vitro: REV1 inserts dC opposite the lesion and DNA polymerase k potentially catalyzes extension reaction from the 3'-dC terminus. Reviewed

    Fukuda, H., Takamura-Enya, T., Masuda, Y., Nohmi, T., Seki, C., Kamiya, K., Sugimura, T., Masutani, C., Hanaoka, F., and *Nakagama, H.

    J. Biol. Chem.   Vol. 284   page: 25585-25592   2009.9

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  49. Interaction with DNA polymerase h is required for nuclear accumulation of REV1 and suppression of spontaneous mutations in human cells. Reviewed

    Akagi, J., *Masutani, C., Kataoka, Y., Kan, T., Ohashi, E., Mori, T., Ohmori, H., and Hanaoka, F.

    DNA Repair   Vol. 8   page: 585-599   2009.5

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  50. Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases. Reviewed

    Kimura, T., Takeuchi, T., Kumamoto-Yonezawa, Y., Ohashi, E., Ohmori, H., Masutani, C., Hanaoka, F., Sugawara, F., Yoshida, H., and *Mizushina, Y.

    Bioorg. Medicinal Chem.   Vol. 17   page: 1811-1816   2009.3

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  51. Specificity of mutations induced by incorporation of oxidized dNTPs into DNA by human DNA polymerase h. Reviewed

    Hidaka, K., Yamada, M., Kamiya, H., Masutani, C., Harashima, H., Hanaoka, F., and *Nohmi, T.

    DNA Repair   Vol. 7   page: 497-506   2008

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  52. Miscoding property of 2'-deoxyinosine, a nitric oxide-derived DNA adduct, during translesion synthesis catalyzed by human DNA polymerases. Reviewed

    *Yasui, M., Suenaga, E., Koyama, N., Masutani, C., Hanaoka, F., Gruz, P., Shibutani, S., Nohmi, T., Hayashi, M., and Honma, M.

    J. Mol. Biol.   Vol. 377   page: 1015-1023   2008

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  53. Efficient and erroneous incorporation of oxidized DNA precursors by human DNA polymerase h. Reviewed

    Shimizu, M., Gruz, P., Kamiya, H., Masutani, C., Xu, Y., Sugiyama, H., Harashima, H., Hanaoka, F., and Nohmi, T.

    Biochemistry   Vol. 46   page: 5515-5522   2007

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  54. A second PCNA loader complex, Ctf18-RFC, specifically stimulates DNA polymerase h activity. Reviewed

    Shiomi, Y., Masutani, C., Hanaoka, F., Kimura, H., and *Tsurimoto, T.

    J. Biol. Chem.   Vol. 282   page: 20906-20914   2007

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  55. 2-Hydroxy-2'-deoxyadenosine 5'-triphosphate enhances A.T --> C.G mutations caused by 8-hydroxy-2'-deoxyguanosine 5'-triphosphate by suppressing its degradation upon replication in a HeLa extract. Reviewed

    Satou, K., Kasai, H., Masutani, C., Hanaoka, F., Harashima, H., and Kamiya, H.

    Biochemistry   Vol. 46   page: 6639-6646   2007

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  56. DNA polymerase h and q function in the same genetic pathway to generate mutations at A/T during somatic hypermutation of Ig genes. Reviewed

    Masuda, K., Ouchida, R., Hikida, M., Kurosaki, T., Yokoi, M., Masutani, C., Seki, M., Wood, R.D., Hanaoka, F., and O-Wang, J.

    J. Biol. Chem.   Vol. 282   page: 17387-17394   2007

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  57. Deficiency of the Caenorhabditis elegans DNA polymerase h homologue increases sensitivity to UV radiation during germ-line development. Reviewed

    Ohkumo, T., Masutani, C., Eki, T., and Hanaoka, F.

    Cell Struct. Funct.   Vol. 31   page: 29-37   2006

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  58. Ultraviolet B radiation induces epithelial tumors in mice lacking Polh and mesenchymal tumors in mice deficient for Poli. Reviewed

    Ohkumo, T., Kondo, Y., Yokoi, M., Tsukamoto, T., Yamada, A., Sugimoto, T., Kanao, R., Higashi, Y., Kondoh, H., Tatematsu, M., Masutani, C., and Hanaoka, F.

    Mol. Cell. Biol.   Vol. 26   page: 7696-7706   2006

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  59. A human DNA polymerase h complex containing Rad18, Rad6 and Rev1; proteomic analysis and targeting of the complex to the chromatin-bound fraction of cells undergoing replication fork arrest. Reviewed

    Yuasa S., M., Masutani, C., Hirano, A., Cohn, M.A., Yamaizumi, M., Nakatani, Y., and Hanaoka, F.

    Genes Cells   Vol. 11   page: 731-744   2006

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  60. Different mutationsignatures in DNA polymerase h- and MSH6-deficient mice suggest separate roles in antibody diversification. Reviewed

    Martomo, S.A., Yang, W.W., Wersto, R.P., Ohkumo, T., Kondo, Y., Yokoi, M., Masutani, C., Hanaoka, F., and Gearhart, P.J.

    Proc. Natl. Acad. Sci. USA   Vol. 102   page: 8656-8661   2005

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  61. Dual roles for DNA polymerase h in homologous DNA recombination and translesion DNA synthesis. Reviewed

    Kawamoto, T., Araki, K., Sonoda, E., Yamashita, Y.M., Harada, K.K., Kikuchi, K., Masutani, C., Hanaoka, F., Nozaki, K., Hashimoto, N., and Takeda, S.

    Mol. Cell   Vol. 20   page: 793-799   2005

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  62. Error-prone translesion synthesis by human DNA polymerase h on DNA containing deoxyadenosine adducts of 7.8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. Reviewed

    Chiapperino, D., Cai, M., Sayer, J.M., Yagi, H., Kroth, H., Masutani, C., Hanaoka, F., Jerina, D.M., and Cheh, A.M.

    J. Biol. Chem.   Vol. 280   page: 39684-39692   2005

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  63. Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein. Reviewed

    Nishi, R., Okuda, Y., Watanabe, E., Mori, T., Iwai, S., Masutani, C., Sugasawa, K., and Hanaoka, F.

    Mol. Cell. Biol.   Vol. 25   page: 5664-5674   2005

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  64. Preferential cis-syn thymine dimer bypass by DNA polymerase h occurs with biased fidelity. Reviewed

    McCulloch, S.D., Kokoska R.J., Masutani, C., Iwai, S., Hanaoka, F., and Kunkel, T.A.

    Nature   Vol. 428   page: 97-100   2004

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  65. DNA binding properties of human DNA polymerase h: Implication for polymerase switching. Reviewed

    Kusumoto, R., Masutani, C., Simmyo, S., Iwai, S., and Hanaoka, F.

    Genes Cells   Vol. 9   page: 1139-1150   2004

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  66. High-efficiency bypass of DNA damage by human DNA polymerase Q. Reviewed

    Seki, M., Masutani, C., Yang, L.W., Schuffert, A., Iwai, S., Bahar, I., and Wood, R.D.

    EMBO J.   Vol. 23   page: 4484-4494   2004

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  67. Interaction of hREV1 with three human Y-family DNA polymerases. Reviewed

    Ohashi, E., Murakumo, Y., Kanjo, N., Akagi, J., Masutani, C., Hanaoka, F., and Ohmori, H.

    Genes Cells   Vol. 9   page: 523-531   2004

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  68. Translesion synthesis past estrogen-derived DNA adducts by human DNA polymerases h and k. Reviewed

    Suzuki, N., Itoh, S., Poon, K., Masutani, C., Hanaoka, F., Ohmori, H., Yoshizawa, I., and Shibutani, S.

    Biochemistry   Vol. 43   page: 6304-6311   2004

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  69. Chemical synthesis and translesion replication of a cis-syn cyclobutane thymine-uracil dimer. Reviewed

    Takasawa, K., Masutani, C., Hanaoka, F., and Iwai, S.

    Nucl. Acids Res.   Vol. 32   page: 1738-1745   2004

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  70. Palm mutants in DNA polymerases a and h alter DNA replication fidelity and translesion activity. Reviewed

    Niimi, A., Limsirichaikul, S., Yoshida, S., Iwai, S., Masutani, C., Hanaoka, F., Kool, E. T., Nishiyama, Y., and Suzuki, M.

    Mol. Cell. Biol.   Vol. 24   page: 2734-2746   2004

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  71. Erroneous incorporation of oxidized DNA precursors by Y-family DNA polymerases. Reviewed

    Shimizu, M., Gruz, P., Kamiya, H., Kim, S.-R., Pisani, F.M., Masutani, C., Kanke, Y., Harashima, H., Hanaoka, F., and Nohmi, T.

    EMBO Reports   Vol. 4   page: 269-273   2003

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  72. Efficiency of extension of mismatched primer termini across from cisplatin and oxaliplatin adducts by human DNA polymerases b and h in vitro. Reviewed

    Bassett, E., Vaisman, A., Havener, J. M., Masutani, C., Hanaoka, F., and Chaney, S.G.

    Biochemistry   Vol. 42   page: 14197-14206   2003

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  73. Identification and characterization of an intermediate in the alkali degradation of (6-4) photoproduct-containing DNA. Reviewed

    Higurashi, M., Ohtsuki, T., Inase, A., Kusumoto, R., Masutani, C., Hanaoka, F., and Iwai, S.

    J. Biol. Chem.   Vol. 278   page: 51968-51973   2003

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  74. 8-Hydroxyguanine in a mutational hotspot of c-Ha-ras gene causes misreplication, “action-at-a-distance" mutagenesis and inhibition of replication. Reviewed

    Jaloszynski, P., Masutani, C., Hanaoka, F., Perwz, A.B., and Nishimura, S.

    Nucl. Acids Res.   Vol. 31   page: 6085-6095   2003

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  75. 129-derived strains of mice are deficient in DNA polymerase i and have normal immunoglobulin hypermutation. Reviewed

    McDonald, J.P., Frank, E.G., Plosky, B.S., Rogozin, I.B., Masutani, C., Hanaoka, F., Woodgate, R., and Gearhart, P.J.

    J. Exp. Med.   Vol. 198   page: 635-643   2003

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  76. Molecular analysis of mutations in DNA polymerase h in xeroderma pigmentosum-variant patients. Reviewed

    Broughton, B.C., Cordonnier, A., Kleijer, W.J., Jaspers, N.G.J., Fawcett, H., Raams, A., Garritsen, V.H., Stary, A., Avril, M.-F., Boudsocq, F., Masutani, C., Hanaoka, F., Fuchs, R.P., Sarasn, A., and Lehmann, A.R.

    Proc. Natl. Acad. Sci. USA   Vol. 99   page: 815-820   2002

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  77. Frameshifts and deletions during in vitro translesion synthesis past Pt-DNA adducts by DNA polymerase b and h. Reviewed

    Bassett, E., Vaisman, A., Tropea, K.A., McCall, C.M., Masutani, C., Hanaoka, F., and Chaney, S.G.

    DNA Repair   Vol. 1   page: 1003-1016   2002

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  78. Detection of reduced RNA synthesis in UV-irradiated Cockayne syndrome group B cells using an isolated nuclear system. Reviewed

    Yamada, A., Masutani, C., and Hanaoka, F.

    Biochim. Biophys. Acta   Vol. 1592   page: 129-134   2002

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  79. The carboxy-terminal domain of the XPC protein plays a crucial role in nucleotide excision repair through interactions with transcription factor IIH. Reviewed

    Uchida, A., Sugasawa, K., Masutani, C., Dohmae, N., Araki, M., Yokoi, M., Ohkuma, Y., and Hanaoka, F.

    DNA Repair   Vol. 1   page: 449-461   2002

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  80. Translesion synthesis by human DNA polymerase h across thymine glycol lesions. Reviewed

    Kusumoto, R., Masutani, C., Iwai, S., and Hanaoka, F.

    Biochemistry   Vol. 41   page: 6090-6099   2002

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  81. Preferential misincorporation of purine nucleotides by human DNA polymerase h opposite benzo[a]pyrene 7,8-diol 9,10-epoxide deoxyguanosine adducts. Reviewed

    Chiapperino, D., Kroth, H., Kramarczuk, I. H., Sayer, J.M., Masutani, C., Hanaoka, F., Jerina, D.M., and Cheh, A.M.

    J. Biol. Chem.   Vol. 277   page: 11765-11771   2002

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  82. Proofreading of DNA polymerase h-dependent replication errors. Reviewed

    Bebenek, K., Matsuda, T., Masutani, C., Hanaoka, F., and Kunkel, T.A.

    J. Biol. Chem.   Vol. 276   page: 2317-2320   2001

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  83. A multistep damage recognition mechanism for global genomic nucleotide excision repair. Reviewed

    Sugasawa, K., Okamoto, T., Shimizu, Y., Masutani, C., Iwai, S., and Hanaoka, F.

    Genes Dev.   Vol. 15   page: 507-521   2001

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  84. Diversity of the damage recognition step in the global genomic nucleotide excision repair in vitro. Reviewed

    Kusumoto, R., Masutani, C., Sugasawa, K., Iwai, S., Araki, M., Uchida, A., Mizukoshi, T., and Hanaoka, F.

    Mutation Res.   Vol. 485   page: 219-227   2001

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  85. Oxygen free-radical damage to DNA: translesion synthesis by human DNA polymerase h and resistance to exonuclease action at cyclopurine deoxynucleoside residues. Reviewed

    Kuraoka, I., Robins, P., Masutani, C., Hanaoka, F., Gasparutto, D., Cadet, J., Wood, R.D., and Lindahl, T.

    J. Biol. Chem.   Vol. 276   page: 49283-49288   2001

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  86. Error rate and specificity of human and murin DNA polymerase h. Reviewed

    Matsuda, T., Bebenek, K., Masutani, C., Rogozin, I.B., Hanaoka, F., and Kunkel, T.A.

    J. Mol. Biol.   Vol. 312   page: 335-346   2001

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  87. Translesion DNA synthesis catalyzed by human pol h and pol k across 1,N6-ethenodeoxyadenosine. Reviewed

    Levine, R.L., Miller, H., Grollman, A., Ohashi, E., Ohmori, H., Masutani, C., Hanaoka, F., and Moriya, M.

    J. Biol. Chem.   Vol. 276   page: 18717-18721   2001

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  88. Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair. Reviewed

    Araki, M., Masutani, C., Takemura, M., Uchida, A., Sugasawa, K., Kondo, J., Ohkuma, Y., and Hanaoka, F.

    J. Biol. Chem.   Vol. 276   page: 18665-18672   2001

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  89. Mutagenic and non-mutagenic bypass of DNA lesions by Drosophila DNA polymerases dpolh and dpoli. Reviewed

    Ishikawa, T., Uematsu, N., Mizukoshi, T., Iwai, S., Iwasaki, H., Masutani, C., Hanaoka, F., Ueda, R., Ohmori, H., and Todo, T.

    J. Biol. Chem.   Vol. 276   page: 15155-15163   2001

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  90. ATP-dependent chromatin remodeling facilitates nucleotide excision repair of UV-induced DNA lesions in synthetic dinucleosomes. Reviewed

    Ura, K., Araki, M., Saeki, H., Masutani, C., Ito, T., Iwai, S., Mizukoshi, T., Kaneda, Y., and Hanaoka, F.

    EMBO J.   Vol. 20   page: 2004-2014   2001

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  91. Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene. Reviewed

    Yuasa, M., Masutani, C., Eki, T., and Hanaoka, F.

    Oncogene   Vol. 19   page: 4721-4728   2000

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  92. 3-methyladenine-DNA glycosylase (MPG protein) interacts with human RAD23 proteins. Reviewed

    Miao, F., Bouziane, M., Dammann, R., Masutani, C., Hanaoka, F., Pfeifer, G., and O'Connor, T.R.

    J. Biol. Chem.   Vol. 275   page: 28433-28438   2000

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  93. Error-prone bypass of certain DNA lesions by the human DNA polymerase h. Reviewed

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

    Genes Dev.   Vol. 14   page: 1589-1594   2000

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  94. Complementation of defective translesion synthesis and ultraviolet light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase h. Reviewed

    Yamada, A., Masutani, C., Iwai, S., and Hanaoka, F.

    Nucl. Acids Res.   Vol. 28   page: 2473-2480   2000

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  95. Modulation of TFIIH-associated kinase activity by complex formation and its relationship with CTD phosphorylation of RNA polymerase II. Reviewed

    Watanabe, Y., Fujimoto, H., Watanabe, T., Maekawa, T., Masutani, C., Hanaoka, F., and Ohkuma, Y.

    Genes Cells   Vol. 5   page: 407-423   2000

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  96. Low fidelity DNA synthesis by human DNA polymerase h. Reviewed

    Matsuda, T., Bebenek, K., Masutani, C., Hanaoka, F., and Kunkel, T.A.

    Nature   Vol. 404   page: 1011-1013   2000

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  97. Efficient translesion replication past oxaliplatin and cisplatin GpG adducts by human DNA polymerase eta. Reviewed

    Vaisman, A., Masutani, C., Hanaoka, F., and Chaney, S.G.

    Biochemistry   Vol. 39   page: 4575-4580   2000

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  98. The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of TFIIH to damaged DNA. Reviewed

    Yokoi, M., Masutani, C., Maekawa, T., Sugasawa, K., Ohkuma, Y., and Hanaoka, F.

    J. Biol. Chem.   Vol. 275   page: 9870-9875   2000

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  99. Reconstitution of damage DNA excision reaction from SV40 minichromosomes with purified nucleotide excision repair proteins. Reviewed

    Araki, M., Masutani, C., Maekawa, T., Watanabe, Y., Yamada, A., Kusumoto, R., Sakai, D., Sugasawa, K., Ohkuma, Y., and Hanaoka, F.

    Mutation Res.   Vol. 459   page: 147-160   2000

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  100. Interaction of hHR23 with S5a: The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26S proteasome. Reviewed

    Hiyama, H., Yokoi, M., Masutani, C., Sugasawa, K., Maekawa, T., Tanaka, K., Hoeijmakers, J.H.J., and Hanaoka, F.

    J. Biol. Chem.   Vol. 274   page: 28019-28025   1999

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  101. Characterization of DNA recognition by the human UV-damaged-DNA binding protein. Reviewed

    Fujiwara, Y., Masutani, C., Mizukoshi, T., Kondo, J., Hanaoka, F., and Iwai, S.

    J. Biol. Chem.   Vol. 274   page: 20027-20033   1999

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  102. Benzimidazolium triflate-activated synthesis of (6-4) photoproduct-containing oligonucleotides and its application. Reviewed

    Iwai, S., Mizukoshi, T., Fujiwara, Y., Masutani, C., Hanaoka, F., and Hayakawa, Y.

    Nucl. Acids Res.   Vol. 27   page: 2299-2303   1999

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

  103. A new Drosophila ultraviolet light-damaged DNA recognition endonuclease that selectively nicks a (6-4) photoproduct site. Reviewed

    Kai, M., Todo, T., Wada, M., Ryo, H., Masutani, C., Kobayashi, H., Morioka, H., Ohtsuka, E., Hanaoka, F., and Sakaguchi, K.

    Biochim. Biophys. Acta   Vol. 1397   page: 180-188   1998

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  104. Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Reviewed

    Sugasawa, K., Ng, J.M.Y., Masutani, C., Iwai, S., van der Spek, P.J., Eker, A.P.M., Hanaoka, F., Bootsma, D., and Hoeijmakers, J.H.J.

    Mol. Cell   Vol. 2   page: 223-232   1998

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  105. Identification and characterization of XPC-binding domain of hHR23B. Reviewed

    Masutani, C., Araki, M., Sugasawa, K., van der Spek, P.J., Yamada, A., Uchida, A., Maekawa, T., Bootsma, D., Hoeijmakers, J.H.J., and Hanaoka, F.

    Mol. Cell. Biol.   Vol. 17   page: 6915-6923   1997

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  106. Two human homologues of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity. Reviewed

    Sugasawa, K., Ng, J.M.Y., Masutani, C., Maekawa, T., Uchida, A., van der Spek, P.J., Eker, A., Rademakers, S., Visser, C., Aboussekhra, A., Wood, R.D., Hanaoka, F., Bootsma, D., and Hoeijmakers, J.H.J.

    Mol. Cell. Biol.   Vol. 17   page: 6924-6931   1997

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  107. XPC and human homologs of RAD23: intracellular localization and relationship to other nucleotide excision repair complexes. Reviewed

    van der Spek, P.J., Eker, A., Rademakers, S., Visser, C., Sugasawa, K., Masutani, C., Hanaoka, F., Bootsma, D., and Hoeijmakers, J.H.J.

    Nucl. Acids Res.   Vol. 24   page: 2551-2559   1996

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  108. Sequential binding of DNA repair proteins RPA and ERCC1 to XPA in vitro. Reviewed

    Saijo, M., Kuraoka, I., Masutani, C., Hanaoka, F., and Tanaka, K.

    Nucl. Acids Res.   Vol. 24   page: 4719-4724   1996

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  109. c-jun stimulates origin-dependent DNA unwinding by polyomavirus large T antigen. Reviewed

    Ito, K., Asano, M., Hughes, P., Kohzaki, H., Masutani, C., Hanaoka, F., Kerppola, T., Curran, T., Murakami, Y., and Ito, Y.

    EMBO J.   Vol. 15   page: 5636-5646   1996

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  110. HHR23B, a human RAD23 homologue, stimulates XPC protein in nucleotide excision repair in vitro. Reviewed

    Sugasawa, K., Masutani, C., Uchida, A., Maekawa, T., van der Spek, P.J., Bootsma, D., Hoeijmakers, J.H.J., and Hanaoka, F.

    Mol. Cell. Biol.   Vol. 16   page: 4852-4861   1996

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  111. Comparison of incorporation and extension of nucleotides in vitro opposite 8-hydroxyguanine (7,8 dihydro-8-oxoguanine) in hot spots of the c-Ha-ras gene. Reviewed

    Kamiya, H., M-Kamiya, N., Fujimuro, M., Kido, K., Inoue, H., Nishimura, S., Masutani, C., Hanaoka, F., and Ohtsuka, E.

    Jpn. J. Cancer Res.   Vol. 86   page: 270-276   1995

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  112. Stimulation of DNA synthesis by mouse DNA helicase B in a DNA replication system containing eukaryotic replication origins. Reviewed

    Matsumoto, K., Seki, M., Masutani, C., Tada, S., Enomoto, T., and Ishimi, Y.

    Biochemistry   Vol. 34   page: 7913-7922   1995

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  113. 8-Hydroxyadenine (7,8-dihydro-8-oxoadenine) induces misincorporation in in vitro DNA synthesis and mutations in NIH 3T3 cells. Reviewed

    Kamiya, H., Miura, H., M-Kamiya, N., Ishikawa, H., Sakaguchi, T., Inoue, H., Sasaki, T., Masutani, C., Hanaoka, F., Nishimura, S., and Ohtsuka, E.

    Nucl. Acids Res.   Vol. 23   page: 2893-2899   1995

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  114. DNA repair protein XPA binds replication protein A (RPA). Reviewed

    Matsuda, T., Saijo, M., Kuraoka, I., Kobayashi, T., Nakatsu, Y., Nagai, A., Enjoji, T., Masutani, C., Sugasawa, K., Hanaoka, F., Yasui, A., and Tanaka, K.

    J. Biol. Chem.   Vol. 270   page: 4152-4157   1995

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  115. Chromosomal localization of three repair genes: the xeroderma pigmentosum group C gene and two human homologs of yeast RAD23. Reviewed

    van der Spek, P.J., Smit, E.M.E., Beverloo, H.B., Sugasawa, K., Masutani, C., Hanaoka, F., Hoeijmakers, J.H.J., and Hagemeijer, A.

    Genomics   Vol. 23   page: 651-658   1994

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  116. Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homolog of yeast RAD23. Reviewed

    Masutani, C., Sugasawa, K., Yanagisawa, J., Sonoyama, T., Ui, M., Enomoto, T., Takio, K., Tanaka, K., van der Spek, P.J., Bootsma, D., Hoeijmakers, J.H.J., and Hanaoka, F.

    EMBO J.   Vol. 13   page: 1831-1843   1994

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  117. Cell-free repair of UV-damaged simian virus 40 chromosomes in human cell extracts: I. Development of a cell-free system detecting excision repair of UV-irradiated SV40 chromosomes in human cell extracts. Reviewed

    Sugasawa, K., Masutani, C., and Hanaoka, F.

    J. Biol. Chem.   Vol. 268   page: 9098-9104   1993

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  118. Cyclobutane thymine dimers in a ras proto-oncogene hot spot activate the gene by point mutation. Reviewed

    Kamiya, H., Murata, N., Murata, T., Iwai, S., Matsukage, A., Masutani, C., Hanaoka, F., and Ohtsuka, E.

    Nucl. Acids Res.   Vol. 21   page: 2355-2361   1993

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  119. Cell-free repair of UV-damaged simian virus 40 chromosomes in human cell extracts: II. Defective DNA repair synthesis by xeroderma pigmentosum cell extracts. Reviewed

    Masutani, C., Sugasawa, K., Asahina, H., Tanaka, K., and Hanaoka, F.

    J. Biol. Chem.   Vol. 268   page: 9105-9109   1993

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  120. An abasic site analogue activates a c-Ha-ras gene by a point mutation at modified and adjacent positions. Reviewed

    Kamiya, H., Suzuki, M., Komatsu, Y., Miura, H., Kikuchi, K., Sakaguchi, T., Murata, N., Masutani, C., Hanaoka, F., and Ohtsuka, E.

    Nucl. Acids Res.   Vol. 20   page: 4409-4415   1992

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  121. In vitro replication study of modified bases in ras sequences. Reviewed

    Kamiya, H., Sakaguchi, T., Murata, N., Fujimuro, M., Miura, H., Ishikawa, H., Shimizu, M., Inoue, H., Nishimura, S., Matsukage, A., Masutani, C., Hanaoka, F., and Ohtsuka, E.

    Chem. Pharm. Bull.   Vol. 40   page: 2792-2795   1992

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  122. Mouse DNA primase plays the principal role in determination of permissiveness for polyomavirus DNA replication. Reviewed

    Eki, T., Enomoto, T., Masutani, C., Miyajima, A., Takada, R., Murakami, Y., Ohno, T., Hanaoka, F., and Ui, M.

    J. Virol.   Vol. 65   page: 4874-4881   1991

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  123. DNA primase stimulatory factor from mouse FM3A cells has an RNase H activity. Reviewed

    Masutani, C., Enomoto, T., Suzuki, M., Hanaoka, F., and Ui, M.

    J. Biol. Chem.   Vol. 265   page: 10210-10216   1990

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  124. DNA primase-DNA polymerase eta assembly from mouse FM3A cells: purification of constituting enzymes, reconstitution, and analysis of RNA priming as coupled to DNA synthesis. Reviewed

    Suzuki, M., Enomoto, T., Masutani, C., Hanaoka, F., Yamada, M., and Ui, M.

    J. Biol. Chem.   Vol. 264   page: 10065-10071   1989

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Books 26

  1. Translesion DNA synthesis (in "DNA Repair Disorders" edited by Nishigori and Sugasawa)

    Chikahide Masutani, Fumio Hanaoka( Role: Joint author)

    Springer  2019 

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  2. Translesion DNA synthesis

    Masutani C., Hanaoka F.( Role: Sole author)

    DNA Repair Disorders  2018.1  ( ISBN:9789811067211

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    Language:Japanese

    Human DNA polymerase η (pol η) is the gene product that is altered in the variant form of xeroderma pigmentosum. Pol η has a structure that can accommodate the cyclobutane pyrimidine dimer, the most prominent ultraviolet-induced DNA lesion. Pol η catalyzes efficient and accurate translesion DNA synthesis (TLS) under the fine control of systems involving interactions with mono-ubiquitinated proliferating cell nuclear antigen. Pol η can also catalyze TLS past cisplatin lesions, which might contribute to the resistance of tumors to chemotherapy. Other Y-family polymerases, pol ι, pol κ, and REV1, and a B-family polymerase pol ζ can contribute to erroneous TLS past ultraviolet-induced lesions. However, these polymerases also contribute to the maintenance of genomic stability in the presence of their cognate DNA lesions. A-family polymerases, pol θ and pol ν, also have TLS abilities, and pol θ has an important role in an alternative end-joining repair pathway for DNA double-strand breaks, protecting against genomic instability. PrimPol is a protein with DNA polymerase and primase activities that is capable of initiating de novo DNA/RNA synthesis and that also has the capacity to bypass modifications that stall the replisome, by TLS or origin-independent re-priming. This chapter summarizes our current knowledge relating to DNA polymerases that are capable of catalyzing TLS.

    DOI: 10.1007/978-981-10-6722-8_12

    Scopus

  3. Translesion DNA synthesis and damage tolerance pathways

    Masuda Y., Hanaoka F., Masutani C.( Role: Sole author)

    DNA Replication, Recombination, and Repair: Molecular Mechanisms and Pathology  2016.1  ( ISBN:9784431558712

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    One of the critical cellular effects of DNA damage is the impediment of the activity of high-fidelity DNA polymerases for replication. Although DNA repair mechanisms physically remove DNA damage before the initiation of DNA replication, remaining damage DNA can still persist in S phase and inhibit replicative DNA polymerases. To deal with this, cells have developed mechanisms to copy chromosomes with unrepaired DNA damage, known as DNA damage tolerance (DDT) mechanisms. As a consequence of DDT, cells can complete chromosomal duplication even in the presence of low levels of DNA damage. DDT mechanisms have been classified into two pathways: translesion DNA synthesis (TLS) and homology-directed repair. In TLS, specialized TLS DNA polymerases utilize damaged DNA as the template and extend the 3′ end of the stalled primer beyond the damage. In homology-directed repair, the stalled primer anneals with the newly synthesized daughter strand and transiently utilizes the undamaged complementary sequence as a template for DNA synthesis. In this article, we summarize and discuss the molecular mechanisms of the DDT pathways of well-analyzed organisms: Escherichia coli, the budding yeast Saccharomyces cerevisiae, and mammalians.

    DOI: 10.1007/978-4-431-55873-6_11

    Scopus

  4. Translesion DNA synthesis and damage tolerance pathways (in DNA Replication, Recombination, and Repair - Molecular Mechanisms and Pathology" edited by Hanaoka and Sugasawa)

    Yuji Masuda, Fumio Hanaoka, Chikahide Masutani( Role: Joint author)

    Springer  2016 

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  5. DNA polymerase eta (in "Function of Translesion DNA Polymerases in Genome Stability" edited byMariorano and Hoffmann)

    Chikahide Masutani, Rie Kanao, Fumio Hanaoka( Role: Joint author)

    Research Signpost  2015 

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  6. Human DNA polymerase eta and its regulatory mechanisms.

    Masutani, C.( Role: Sole author)

    Genes and Environment  2012 

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  7. 動物細胞の紫外線DNA損傷の修復と複製

    益谷央豪( Role: Sole author)

    蛋白質核酸酵素2009年3月号増刊「染色体サイクル」  2009 

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  8. Xeroderma Pigmentosum Variant, XP-V: its product and biological roles.

    Masutani, C., Hanaoka, F., and *Ahmad, S.I.( Role: Joint author)

    Adv. Exp. Med. Biol.  2008 

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  9. Use of RNAi in C. elegans.

    Ohkumo, T., Masutani, C., Eki, T., and *Hanaoka, F.( Role: Joint author)

    Methods Mol. Biol.  2008 

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  10. 真核細胞のDNA合成酵素pp219-226、プライマーゼ―真核細胞pp260-263

    益谷央豪、花岡文雄( Role: Joint author)

    生物薬科学実験講座8遺伝子II(名取俊二/中西義信・編集 廣川書店)  2003 

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  11. DNAポリメラーゼh:DNA修復欠損遺伝病の研究から損傷乗り越え型DNAポリメラーゼの発見へ

    花岡文雄、益谷央豪( Role: Joint author)

    生化学  2002 

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  12. 真核生物が獲得した天然の日焼け止めクリーム―XP-V群色素性乾皮症遺伝子産物;DNAポリメラーゼh(イータ)について-

    大雲剛志、益谷央豪、花岡文雄( Role: Joint author)

    放射線生物研究  2002 

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  13. 色素性乾皮症バリアントにおける損傷乗り越えDNA複製の異常

    益谷央豪、花岡文雄( Role: Joint author)

    蛋白質核酸酵素(共立出版)増刊『DNA修復ネットワークとその破綻の分子病態』  2001 

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  14. 色素性乾皮症バリアント群の原因遺伝子のクローニング遺伝子医学

    湯浅真弓、益谷央豪、花岡文雄( Role: Joint author)

    メディカルドゥ  2000 

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  15. Xeroderma pigmentosum variant: From a human genetic disorder to a novel DNA polymerase.

    Masutani, C., Kusumoto, R., Yamada, A., Yuasa, M., Araki, M., Nogimori, T., Yokoi, M., Eki, T., Iwai, S., and Hanaoka, F.( Role: Joint author)

    Cold Spring Harbor Symp. Quantit. Biol.  2000 

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  16. バリアント型色素性乾皮症と損傷乗り越えDNA複製

    益谷央豪、花岡文雄( Role: Joint author)

    医学のあゆみ(医歯薬出版)  2000 

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  17. V群色素性乾皮症遺伝子産物 DNAポリメラーゼh(イータ)について

    楠本理加、益谷央豪、花岡文雄( Role: Joint author)

    ファルマシア  2000 

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  18. 損傷を乗り越える新規DNAポリメラーゼ

    山田亜夕美、益谷央豪、花岡文雄( Role: Joint author)

    生化学  2000 

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  19. ヌクレオチド除去修復の分子機構

    荒木真理人、益谷央豪、花岡文雄( Role: Joint author)

    蛋白質核酸酵素(共立出版)  1999 

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  20. 色素性乾皮症研究の最前線-DNA修復欠損と損傷DNA複製欠損

    益谷央豪、花岡文雄( Role: Joint author)

    実験医学(羊土社)  1999 

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  21. 色素性乾皮症バリアント(XPV)遺伝子はDNAポリメラーゼhをコードする

    益谷央豪、花岡文雄( Role: Joint author)

    実験医学(羊土社)  1999 

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  22. 真核細胞のヌクレオチド除去修復

    益谷央豪、花岡文雄( Role: Joint author)

    実験医学(羊土社)  1998 

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  23. DNA修復と細胞周期制御

    横井雅幸、益谷央豪、花岡文雄( Role: Joint author)

    蛋白質核酸酵素(共立出版)  1996 

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  24. 染色体複製の機構

    益谷央豪、花岡文雄( Role: Joint author)

    細胞増殖の制御(豊島久真男編集)南江堂(東京)第2刷  1995 

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  25. 真核細胞のヌクレオチド除去修復

    益谷央豪、菅澤薫、花岡文雄( Role: Joint author)

    細胞工学(秀潤社)  1994 

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  26. 無細胞系を用いたクロマチンDNAの複製と修復

    菅澤薫、益谷央豪、花岡文雄( Role: Joint author)

    実験医学(羊土社)  1993 

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KAKENHI (Grants-in-Aid for Scientific Research) 10

  1. DNA損傷によるDNA複製の阻害と転写の阻害を連携制御するメカニズムの解析

    Grant number:21K19843  2021.7 - 2023.3

    挑戦的研究(萌芽)

    益谷 央豪

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    Authorship:Principal investigator 

    Grant amount:\6500000 ( Direct Cost: \5000000 、 Indirect Cost:\1500000 )

  2. ヒト細胞のDNA損傷トレランスの分子機構と細胞レベルの機能の解析

    Grant number:20H04335  2020.4 - 2023.3

    益谷 央豪

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    Grant amount:\17680000 ( Direct Cost: \13600000 、 Indirect Cost:\4080000 )

    細胞は、ゲノム上に未修復のDNA損傷を残したまま、DNA複製を継続・完了する、DNA損傷トレランスと総称される機構を備えている。ヒト細胞における主要な経路は、DNAポリメラーゼ・イータによる損傷乗り越えDNA合成(TLS: translesion synthesis)であり、その制御機構の解析を行う。DNA損傷トレランスは、DNA複製因子PCNAのモノ‐及びポリ‐ユビキチン化によって制御されるが、さらに、PCNAホモ3量体中の複数の分子が同時に修飾を受けるマルチ‐ユビキチン化により活性化される新経路を見出している。本計画では、この新経路に関わる分子を同定しその機能を解析する。

  3. ヒト細胞のDNA損傷トレランスの連携制御メカニズムの解析

    2016.4

    科学研究費補助金  基盤研究(A)

    益谷 央豪

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  4. analysis of regulatory mechanisms of DNA damage tolerance pathways in human cells

    Grant number:16H01775  2016.4 - 2020.3

    Masutani Chikahide

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    Grant amount:\41340000 ( Direct Cost: \31800000 、 Indirect Cost:\9540000 )

    We demonstrated the relevance of three PCNA interacting peptide motifs of Pol eta for the regulation of translesion DNA synthesis in human cells. We also identified a region, which is different from the previous report, of Pol eta to interact with RAD18. We reported the molecular mechanisms of mono- and poly-ubiquitination reactions of PCNA by usisng reconstituted in vitro systems. Then, molecular mechanism of the deubiquitination reaction by USP7 is also demonstrated. Finally, we constituted the system to analyse the DNA damage tolerance pathway regulated by the multiple modifications of a PCNA homo trimer.

  5. DNA損傷による複製阻害を回避するメカニズムの包括的理解

    2013.4 - 2016.3

    科学研究費補助金  基盤研究(A)

  6. Biochemical study on the molecular mechanisms of induced mutagenesis and post-replication repair pathways

    Grant number:24310040  2012.4 - 2015.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Masuda Yuji, MASUTANI Chikahide, Kanao Rie

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    Radiation and environmental mutagens induce mutations. To elucidate molecular mechanisms of the induced mutagenesis is one of the biggest issues in this field. A large fraction of the induced mutation is generated by a cellular process, post-replication repair pathway. In humans, cells have two sub-pathways. One is the error-prone pathway, translesion DNA synthesis (TLS). The other is the error-free, in principle, pathway, template switch (TS). The regulation of the pathway choice that is a crucial step for the maintenance of genetic stability is regulated by ubiquitination of PCNA. In this study, we established in vitro reconstitution systems for PCNA ubiquitination and deubiquitination, and analyzed molecular mechanisms of these biochemical reactions.

  7. Crosstalk of translesion synthesis and checkpoint mechanisms

    Grant number:24651045  2012.4 - 2014.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    MASUTANI Chikahide, KANAO Rie

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    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

    Human Polh is the responsible gene product of xeroderma pigmentosum variant, a cancer prone syndrome. Polh catalyzes translesion DNA synthesis (TLS) past the most prominent UV-induced DNA lesion, cyclobutane pyrimidine dimer (CPD), very efficiently. On the other hand, Polh is unable to bypass another UV-induced DNA lesion, 6-4 photoproduct, resulting in the activation of cell cycle checkpoint mechanisms. This project aimes to address the relations between TLS and cell cycle checkpoint mechanisms. Expression of Polh or PCNA mutants affected cell cycle checkpoint, suggesting a linkage of TLS and checkpoint mechanisms in human cells.

  8. Generality of translesion synthesis coupling replication and repair

    Grant number:22131008  2010.4 - 2015.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    HANAOKA FUMIO, MASUTANI Chikahide, YOKOI Masayuki

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    In order to examine the generality of translesion synthesis (TLS), which coordinates replication and repair, we analyzed the structure of co-crystals of human DNA polymerase eta (Pol eta) and CPD-containing DNA with X-ray diffraction. We found that human Pol eta acts like a molecular splint to stabilize damaged DNA in a normal B-form conformation. On the other hand, the crystal structure of human Pol eta and cisplatin-containing DNA revealed that Pol eta could not act like a molecular splint. Mono- or polyubiquitination of PCNA controls the pathway choice of DNA damage tolerance. We demonstrated that PCNA is poly-ubiquitinated via transfer of a pre-formed ubiquitin chain on monoubiquitinated PCNA.

  9. タンパク質のマルチ翻訳後修飾による損傷乗り越えDNA複製の制御

    2010.4 - 2012.3

    科学研究費補助金  基盤研究(B)

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  10. 損傷乗り越え複製後のDNA損傷の修復と娘細胞への分配

    Grant number:21651020  2009 - 2010

    科学研究費助成事業  挑戦的萌芽研究

    益谷 央豪

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    Authorship:Principal investigator 

    Grant amount:\3200000 ( Direct Cost: \3200000 )

    紫外線照射により主に2種類のDNA損傷が生じることが知られている。6-4光産物は、ヌクレオチド除去修復機構により効率よく認識されて比較的速やかに修復される。しかし、シクロブタン型ピリミジン2量体(CPD)は、たいへん修復されにくいことが知られている。本応募者らは、高発癌性遺伝疾患である色素性乾皮症C群の責任遺伝子産物複合体が、6-4光産物の認識において中心的な役割を果たし、ヌクレオチド除去修復に関わること、また、バリアント群の責任遺伝子産物として、ヒトDNAポリメラーゼ・イータ(Polη)を同定し、PolηがCPDを鋳型として乗り越えて複製することを明らかにしてきた。今日までに、転写の妨げとなったDNA損傷を優先的に修復する機構は知られているが、複製と修復の連携機構は知られていない。そこで、本年度は、複製の妨げとなったDNA損傷の修復を検出するための条件を設定するために、細胞周期をG1/S期に同調したヒト細胞に紫外線を照射し、S期の進行をFACSにより調べた。その結果、ヌクレオチド除去修復及びPolηが正常な細胞株では、4J/m2程度の紫外線照射では、S期の進行に顕著な遅延は認められないこと、8J/m2では遅延は認められるものの、最終的にはS期を通過できることを明らかにした。一方で、Polηを欠損した色素性乾皮症バリアント群患者由来の細胞株では、2J/m2の紫外線照射でも顕著なS期の進行遅延が認められた。さらに、DNA複製スライディング・クランプであるPCNAの164番目のリジンをアルギニンに置換したヒト細胞系を構築して検討した結果、この細胞ではPolη欠損細胞と同程度の顕著なS期の進行遅延が認められることを明らかにした。

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Teaching Experience (On-campus) 1

  1. Natural Environment and the Human Being

    2011