Updated on 2021/04/09

写真a

 
MASUDA Yuji
 
Organization
Nagoya University Graduate School of Medicine Program in Integrated Medicine Molecular Pharmacology Associate professor
Title
Associate professor
Contact information
メールアドレス

Degree 1

  1. 博士(農学) ( 1995.3   東京大学 ) 

Research Areas 1

  1. Others / Others  / 生化学

Research History 7

  1. 名古屋大学大学院医学研究科総合医学専攻・准教授           名古屋大学環境医学研究所・准教授

    2013.5

      More details

    Country:Japan

  2. 名古屋大学環境医学研究所・准教授

    2011.10 - 2013.4

      More details

    Country:Japan

  3. 広島大学原爆放射線医科学研究所・助教

    2007.4 - 2011.9

      More details

    Country:Japan

  4. 広島大学原爆放射線医科学研究所・助手

    2002.4 - 2007.3

      More details

    Country:Japan

  5. 広島大学原爆放射能医学研究所・助手

    1998.7 - 2002.3

      More details

    Country:Japan

  6. ハーバード大学公衆衛生大学院・博士研究員

    1996.9 - 1998.6

      More details

    Country:United States

  7. 奈良先端科学技術大学院大学バイオサイエンス研究科・教務職員

    1995.4 - 1996.8

      More details

    Country:Japan

▼display all

Education 2

  1. The University of Tokyo

    - 1995.3

      More details

    Country: Japan

  2. Saitama University   Faculty of Science

    1986.4 - 1990.3

      More details

    Country: Japan

Professional Memberships 5

  1. 日本遺伝学会

  2. 日本癌学会

  3. 日本放射線影響学会

  4. 日本分子生物学会

  5. 環境変異原学会

Awards 4

  1. 日本遺伝学会第88回大会 ベストペーパー賞

    2017.3   日本遺伝学会  

     More details

    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  2. 日本遺伝学会第83回大会 ベストペーパー賞

    2012.3   日本遺伝学会  

     More details

    Country:Japan

  3. 日本遺伝学会第82回大会 ベストペーパー賞

    2011.3   日本遺伝学会  

     More details

    Country:Japan

  4. 日本遺伝学会奨励賞

    2008   日本遺伝学会  

     More details

    Country:Japan

 

Papers 18

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

    Masuda Y, Saeki Y, Arai N, Kawai H, Kukimoto I, Tanaka K, Masutani C

    The Journal of biological chemistry   Vol. 294 ( 41 ) page: 14860-14875   2019.10

     More details

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

    DOI: 10.1074/jbc.RA119.008374

    PubMed

  2. Spatiotemporal regulation of PCNA ubiquitination in damage tolerance pathways

    Masuda Yuji, Masutani Chikahide

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

     More details

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

    DOI: 10.1080/10409238.2019.1687420

    Web of Science

    PubMed

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

    Masuda Yuji, Kanao Rie, Kawai Hidehiko, Kukimoto Iwao, Masutani Chikahide

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 294 ( 11 ) page: 4177-4187   2019.3

     More details

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

    DOI: 10.1074/jbc.RA118.005167

    Web of Science

    PubMed

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

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

    Nucleic acids research     2018.10

     More details

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

    DOI: 10.1093/nar/gky943

    PubMed

  5. Overexpression of Rev1 promotes the development of carcinogen-induced intestinal adenomas via accumulation of point mutation and suppression of apoptosis proportionally to the Rev1 expression level. Reviewed

    Sasatani M, Xi Y, Kajimura J, Kawamura T, Piao J, Masuda Y, Honda H, Kubo K, Mikamoto T, Watanabe H, Xu Y, Kawai H, Shimura T, Noda A, Hamasaki K, Kusunoki Y, Zaharieva EK, Kamiya K*

    Carcinogenesis. 2017 May 1;38(5):570-578. doi: 10.1093/carcin/bgw208.   Vol. 38 ( 5 ) page: 570-578   2017.5

     More details

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

    DOI: doi: 10.1093/carcin/bgw208

  6. 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* (#: co-first author)

    Cell Rep.   Vol. 13 ( 10 ) page: 2072-2080   2015.12

     More details

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

    DOI: 10.1016/j.celrep.2015.11.014

  7. Short CCG repeat in huntingtin gene is an obstacle for replicative DNA polymerases, potentially hampering progression of replication fork. Reviewed

    Le HP, Masuda Y, Tsurimoto T, Maki S, Katayama T, Furukohri A*, Maki H

    Genes Cells   Vol. 20 ( 10 ) page: 817-833   2015.10

     More details

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

    DOI: 10.1111/gtc.12275

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

    Masuda Y#, Kanao R#, Kaji K, Ohmori H, Hanaoka F, Masutani C* (#: co-first author)

    Nucleic Acids Res.   Vol. 43 ( 16 ) page: 7898-7910   2015.9

     More details

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

    DOI: 43(16):7898-910

  9. Repair synthesis step involving ERCC1-XPF participates in DNA repair of the Top1-DNA damage complex Reviewed

    Takahata C, Masuda Y, Takedachi A, Tanaka K, Iwai S and Kuraoka I*

    Carcinogenesis   Vol. 36 ( 8 ) page: 841–851   2015.5

     More details

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

    DOI: 10.1093/carcin/bgv078

  10. Relevance of Simultaneous Mono-Ubiquitinations 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. 9:e104279. 2014.   Vol. 10   page: e0118775   2015.2

     More details

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

    DOI: 10.1371/journal.pone.0118775

  11. A Novel ATM/TP53/p21-Mediated Checkpoint Only Activated by Chronic γ-Irradiation. Reviewed

    Cao L, Kawai H*, Sasatani M, Iizuka D, Masuda Y, Inaba T, Suzuki K, Ootsuyama A, Umata T, Kamiya K, Suzuki F.

    PLoS One. 9:e104279. 2014.   Vol. 9   page: e104279   2014.8

     More details

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

    DOI: DOI: 10.1371/journal.pone.0104279

  12. Guanine-5-carboxylcytosine base pairs mimic mismatches during DNA replication. Reviewed

    Shibutani T, Ito S, Toda M, Kanao R, Collins LB, Shibata M, Urabe M, Koseki H, Masuda Y, Swenberg JA, Masutani C, Hanaoka F, Iwai S, Kuraoka I.*

    Sci Rep.   Vol. 4   page: 5220   2014.6

     More details

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

    DOI: DOI: 10.1038/srep05220

  13. A novel interplay between the Fanconi anemia core complex and ATR-ATRIP kinase during DNA cross-link repair. Reviewed

      Vol. 41 ( 14 ) page: 6930-6941   2013.5

     More details

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

    DOI: 10.1093/nar/gkt467

  14. Strand breakage of (6–4) photoproduct-containing DNA at neutral pH and its repair by the ERCC1–XPF protein complex. Reviewed

      Vol. 11 ( 21 ) page: 3526-3534   2013.3

     More details

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

    DOI: 10.1039/c3ob00012e

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

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

    Nucleic Acids Res.     2012.8

     More details

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

    DOI: 10.1093/nar/gks763

  16. In Vitro Studies of Exchanges between Replicative and Translesion DNA Polymerases in the Eukaryotic Post-replication Repair Pathway Invited Reviewed

    Masuda Y*

    Genes and Environment   Vol. 34 ( 2 ) page: 70-76   2012.5

     More details

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

    DOI: 10.3123/jemsge.34.70

  17. Molecular nature of radiation injury and DNA repair disorders associated with radiosensitivity. Invited Reviewed

    Masuda Y, Kamiya K*

    International Journal of Hematology   Vol. 95 ( 3 ) page: 239-245   2012.3

     More details

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

    DOI: DOI 10.1007/s12185-012-1008-y

  18. Asymmetric nature of two subunits of RAD18, a RING-type ubiquitin ligase E3, in the human RAD6A-RAD18 ternary complex Reviewed

    Masuda Y*, Suzuki M, Kawai H, Suzuki F, Kamiya K.

    Nucleic Acids Research   Vol. 40 ( 3 ) page: 1065-1076   2012.2

     More details

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

    RAD18, a RING-type ubiquitin ligase (E3) that plays an essential role in post-replication repair, possesses distinct domains named RING, UBZ, SAP and the RAD6-binding domain (R6BD) and forms a dimer. RAD6, an ubiquitin-conjugating enzyme (E2), stably associates with R6BD in the C-terminal portion. In this study, we established a method to distinguish between the two subunits of RAD18 by introduction of different tags, and analyzed mutant complexes. Our results, surprisingly, demonstrate that RAD6A and RAD18 form a ternary complex, RAD6A-(RAD18)(2) and the presence of only one R6BD in the two RAD18 subunits is sufficient for ternary complex formation and the ligase activity. Interestingly, ligase activity of a mutant dimer lacking both R6BDs is not restored even with large amounts of RAD6A added in solution, suggesting a requirement for precise juxtaposition via interaction with R6BD. We further show that mutations in both subunits of either RING or SAP, but not UBZ, strongly reduce ligase activity, although inactivation in only one of two subunits is without effect. These results suggest an asymmetric nature of the two RAD18 subunits in the complex.

▼display all

Research Project for Joint Research, Competitive Funding, etc. 2

  1. チェックポイント機能を欠如したがん細胞特異的に化学療法の効果を増感させる薬剤の開発

    2011.12 - 2012.7

    研究成果最適展開支援プログラムA-STEPフィージビリティスタディステージ 探索タイプ 

      More details

    Grant type:Competitive

  2. 哺乳類での突然変異誘発の分子機構の解明

    2003.4 - 2007.3

    特色ある大学教育支援プログラム 

      More details

    Grant type:Competitive

KAKENHI (Grants-in-Aid for Scientific Research) 8

  1. 誘発変異頻度を規定する損傷トレランス経路の時空間的制御の分子基盤の確立

    2018.4

    科学研究費補助金  基盤研究(B)

    増田雄司

  2. 誘発変異頻度を規定する損傷トレランス経路の時空間的制御の分子基盤の確立

    Grant number:18H03371  2018.4 - 2022.3

    増田 雄司

      More details

    Authorship:Principal investigator 

    Grant amount:\17160000 ( Direct Cost: \13200000 、 Indirect Cost:\3960000 )

    放射線や環境変異原によって引き起こされる重要な生物影響の一つは変異の誘発であり、 その分子機構の解明は当該研究分野の重要課題である。誘発変異の主要な原因となる損傷トレランス機構は、損傷のあるゲノムDNAの複製を、損傷を除去することなく完了する分子機構であり、 二つのサブ経路「忠実度の低い損傷乗り越えDNAポリメラーゼを介したTranslesion DNA synthes is(TLS)」と 「忠実度の高いDNAポリメラーゼ を介したTemplate switch (TS)」が存在し、DNA複製の補助因子であるPCNAのユビキチン化によって制御される。損傷部位でのTLSまたはTSへの振り分けは、変異誘発リスクに直結し、遺伝的安定性の維持に極めて重要である。本研究では、ユビキチン化PCNAを標的とする様々な因子の機能解析を通してTLSとTSの振り分けメカニズムを明らかにすることで、変異誘発のリスクを最適化する分子機構の解明を目指している。
    本研究は、次の三つの課題、1) ポリユビキチン化PCNAと相互作用する新規なTS制御因子の解析、 2) ポリユビキチン化PCNAの脱ユビキチン酵素の同定と機能解析、3) PCNAのポリユビキチン化酵素、HLTFによるPCNAのポリユビキチン化の時空間的制御機構の解析、に焦点をしぼり研究 を推進している。本年度はそれぞれの課題について次の通り研究を行った。
    1) ポリユビキチン化PCNAと相互作用する新規制御因子、PPIF破壊細胞の解析を行った。2) 前年度に引き続き、HeLa細胞の抽出液中に見出されたポリユビキチン化PCNAの脱ユビキチン酵素活性の精製を進めた。3) DNA損傷を与える薬剤で処理した細胞の各細胞周期におけるHLTFの動態を解析した。また、前年度に樹立したHLTF破壊細胞株の薬剤感受性について検討した。
    研究成果の一部を論文に纏め発表した。
    計画通りに研究を推進する。

  3. Multiple mechanisms of post-replication repair pathway choice by deubiquitinases for ubiquitinated PCNA

    Grant number:16K12594  2016.4 - 2018.3

    MASUDA Yuji

      More details

    Authorship:Principal investigator 

    Grant amount:\3770000 ( Direct Cost: \2900000 、 Indirect Cost:\870000 )

    The DNA damage tolerance pathways as the post-replication repair are regulated by ubiquitination of proliferating cell nuclear antigen (PCNA). Since mono- and poly-ubiquitination of PCNA stimulates the error-prone pathway, translesion DNA synthesis (TLS), and the error-free, in principle, pathway, template switch (TS), respectively. However, in humans, the regulatory mechanism is obscure because poly-ubiquitinated PCNA is only slightly detectable. In this study, we identified deubiquitinases for ubiquitinated PCNA and analyzed their functions in the damage tolerance pathways.

  4. Biochemical study of damage tolerance pathways to control the induced mutagenesis

    Grant number:15H02818  2015.4 - 2019.3

    Masuda Yuji

      More details

    Authorship:Principal investigator 

    Grant amount:\12610000 ( Direct Cost: \9700000 、 Indirect Cost:\2910000 )

    Mutagenesis is one of the critical outcomes of exposure by radiation or environmental mutagens. The molecular mechanism of the induced mutagenesis, which is one of the most important issues in this field, remains to be elucidated. A significant fraction of the induced mutation is generated through a cellular process, so-called DNA damage tolerance. In humans, two sub-pathways are regulated by ubiquitination of PCNA, one of the auxiliary factors of DNA replication; one is the error-prone pathway, translesion DNA synthesis, inducing point mutations, and the other is template switch, which is the error-free, in principle, but has a risk of genomic rearrangements. Therefore the regulation of the choice of two pathways is a crucial step for the maintenance of genetic stability. In this study, we examined the molecular mechanisms of the pathway choice by analysis of factors involved in the PCNA ubiquitination.

  5. 誘発突然変異頻度を適切に制御する損傷トレランス経路の生化学的分子基盤の確立

    2015.4 - 2018.3

    科学研究費補助金  基盤研究(B)

      More details

    Authorship:Principal investigator 

  6. PCNAの新規脱ユビキチン酵素群の同定と複製後修復経路の多重制御メカニズム

    2014.4 - 2016.3

    科学研究費補助金 

  7. 誘発突然変異と複製後修復経路の制御機構の解明に向けた生化学的分子基盤の確立

    2012.4 - 2015.3

    科学研究費補助金  基盤研究(B)

      More details

    Authorship:Principal investigator 

  8. 突然変異誘発に関与する複製後修復経路の分子機構の解明に向けた生化学的基盤の確立

    2008.4 - 2012.3

    科学研究費補助金  基盤研究(B)

      More details

    Authorship:Principal investigator 

▼display all