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Generality of translesion synthesis coupling replication and repair

Planned Research

Project AreaCoupling of replication, repair and transcription, and their common mechanism of chromatin remodeling
Project/Area Number 22131008
Research Category

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

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionGakushuin University

Principal Investigator

HANAOKA FUMIO  学習院大学, 理学部, 教授 (50012670)

Co-Investigator(Kenkyū-buntansha) MASUTANI Chikahide  名古屋大学, 環境医学研究科, 教授 (40241252)
Co-Investigator(Renkei-kenkyūsha) YOKOI Masayuki  学習院大学, 理学部, 助教 (00322701)
Project Period (FY) 2010-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥188,500,000 (Direct Cost: ¥145,000,000、Indirect Cost: ¥43,500,000)
Fiscal Year 2014: ¥36,140,000 (Direct Cost: ¥27,800,000、Indirect Cost: ¥8,340,000)
Fiscal Year 2013: ¥37,830,000 (Direct Cost: ¥29,100,000、Indirect Cost: ¥8,730,000)
Fiscal Year 2012: ¥39,650,000 (Direct Cost: ¥30,500,000、Indirect Cost: ¥9,150,000)
Fiscal Year 2011: ¥39,260,000 (Direct Cost: ¥30,200,000、Indirect Cost: ¥9,060,000)
Fiscal Year 2010: ¥35,620,000 (Direct Cost: ¥27,400,000、Indirect Cost: ¥8,220,000)
Keywords損傷乗り越え合成 / 紫外線 / 色素性乾皮症 / DNAポリメラーゼ / PCNA / ユビキチン / 損傷トレランス / X線結晶構造解析 / DNAポリメラーゼη / スフィンゴシン / XPV / モデルマウス / シャトルベクター / 突然変異 / DNA損傷トレランス / 体細胞超突然変異 / WAモチーフ / ピリミジン二量体 / 紫外線損傷 / シスプラチン / 損傷乗り越え複製 / 翻訳後修飾 / REV1 / Hsp90 / モノユビキチン化PCNA / DNAポリメラーゼ・イータ / CPD / X線結晶構造 / DNAポリメラーゼ・ゼータ / ニワトリDT40
Outline of Final Research Achievements

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.

Report

(6 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (44 results)

All 2015 2014 2013 2012 2011 2010 Other

All Journal Article (22 results) (of which Peer Reviewed: 22 results,  Open Access: 8 results,  Acknowledgement Compliant: 9 results) Presentation (20 results) (of which Invited: 19 results) Remarks (2 results)

  • [Journal Article] Both high-fidelity replicative and low-fidelity Y-family polymerases are involved in DNA rereplication.2015

    • Author(s)
      Sekimoto T, Oda T, Kurashima K, Hanaoka F, Yamashita T
    • Journal Title

      Mol Cell Biol

      Volume: 35 Issue: 4 Pages: 699-715

    • DOI

      10.1128/mcb.01153-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Functional regulation of the DNA damage-recognition factor DDB2 by ubiquitination and interaction with xeroderma pigmentosum group C protein.2015

    • Author(s)
      Syota Matsumoto, Eric S. Fischer, Takeshi Yasuda, Naoshi Dohmae, Shigenori Iwai, Toshio Mori, Ryotaro Nishi, Ken-ichi Yoshino, Wataru Sakai, Fumio Hanaoka, Nicolas H. Thoma, Kaoru Sugasawa
    • Journal Title

      Nucleic Acids Research

      Volume: 3 Issue: 3 Pages: 1700-1713

    • DOI

      10.1093/nar/gkv038

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relevance of simultaneous mono-ubiquitinations of multiple units of PCNA homo-trimers in DNA damage tolerance.2015

    • Author(s)
      Kanao R, Masuda Y, Deguchi S, Yumoto-Sugimoto M, Hanaoka F, Masutani C
    • Journal Title

      PLoS One

      Volume: 10 Issue: 2 Pages: e0118775-e0118775

    • DOI

      10.1371/journal.pone.0118775

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Shingosine, a modulator of human translesion DNA polymerase activity.2014

    • Author(s)
      Kamath-Loeb AS, Balakrishna S, Whittington D, Shen JC, Emond MJ, Okabe T, Masutani C, Hanaoka F, Nishimura S, Loeb LA
    • Journal Title

      J Biol Chem

      Volume: 289 Issue: 31 Pages: 21663-21672

    • DOI

      10.1074/jbc.m114.570242

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Remarkable induction of UV-signature mutations at the 3'-cytosine of dipyrimidine sites except at 5'-TCG-3' in the UVB-exposed skin epidermis of xeroderma pigmentosum variant model mice.2014

    • Author(s)
      Ikehata H, Chang Y, Yokoi M, Yamamoto M, Hanaoka F
    • Journal Title

      DNA Repair

      Volume: 22 Pages: 112-122

    • DOI

      10.1016/j.dnarep.2014.07.012

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A cyclobutane thymine-N4-methylcytosine dimer is resistant to hydrolysis but strongly blocls DNA synthesis.2014

    • Author(s)
      Yamamoto J, Oyama T, Kunishi T, Masutani C, Hanaoka F, Iwai S
    • Journal Title

      Nucleic Acids Res

      Volume: 42 Issue: 3 Pages: 2075-2084

    • DOI

      10.1093/nar/gkt1039

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Guanine-5-carboxylcytosine base pairs mimic mismatches during DNA replication.2014

    • Author(s)
      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
    • Journal Title

      Scientific Reports

      Volume: 4 Issue: 1 Pages: 5220-5220

    • DOI

      10.1038/srep05220

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Trapping DNA replication origins from the human genome.2013

    • Author(s)
      Eki T, Murakami Y, Hanaoka F
    • Journal Title

      Genes (Basel)

      Volume: 4 Issue: 2 Pages: 198-225

    • DOI

      10.3390/genes4020198

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mechanism of somatic hypermutation at the WA motif by human DNA polymerase eta.2013

    • Author(s)
      Zhao Y, Gregory MT, Biertümpfel C, Hua YJ, Hanaoka F, Yang W
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 110 Issue: 20 Pages: 8146-8151

    • DOI

      10.1073/pnas.1303126110

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Structure-function analysis of the EF-hand protein centrin-2 for its intracellular localization and nucleotide excision repair.2013

    • Author(s)
      Nishi R, Sakai W, Tone D, Hanaoka F, Sugasawa K
    • Journal Title

      Nucleic Acids Res

      Volume: 41 Issue: 14 Pages: 6917-6929

    • DOI

      10.1093/nar/gkt434

    • NAID

      120005621886

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Identification of new scavengers for hydroxyl radicals and superoxide dismutase by utilising ultraviolet A photoreaction of 8-methoxysoralen and a variety of mutants of Escherichia coli: implications on certain diseases of DNA repair deficiency.2012

    • Author(s)
      Ahmad SI
    • Journal Title

      J Photochem Photobiol B

      Volume: 116 Pages: 30-36

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis of human DNA polymerase eta-mediated chemoresistance to cisplatin.2012

    • Author(s)
      Zhao Y
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 109 Issue: 19 Pages: 7269-7274

    • DOI

      10.1073/pnas.1202681109

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A DNA oligomer containing 2,2,4-triamino-5(2H)-oxazolone is incised by human NEIL1 and NTH1.2012

    • Author(s)
      Kino K
    • Journal Title

      Mutat Res

      Volume: 734 Issue: 1-2 Pages: 73-77

    • DOI

      10.1016/j.mrfmmm.2012.03.007

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The vital role of polymerase ζ and REV1 in mutagenic, but not correct, DNA synthesis across benzo[a]pyrene-dG and recruitment of polymerase ζ by REV1 to replication-stalled site.2012

    • Author(s)
      Hashimoto K
    • Journal Title

      J Biol Chem

      Volume: 287 Issue: 12 Pages: 9613-9622

    • DOI

      10.1074/jbc.m111.331728

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stalled Polη at its cognate substrate initiates an alternative translesion synthesis pathway via interaction with REV1.2012

    • Author(s)
      Ito W
    • Journal Title

      Genes Cells

      Volume: 17 Issue: 2 Pages: 98-108

    • DOI

      10.1111/j.1365-2443.2011.01576.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of mice deficient in both REV1 catalytic activity and POLH reveals an unexpected role for POLH in the generation of C to G and G to C transversions during Ig gene hypermutation.2012

    • Author(s)
      Kano C
    • Journal Title

      Int Immunol

      Volume: 24 Issue: 3 Pages: 169-174

    • DOI

      10.1093/intimm/dxr109

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation2011

    • Author(s)
      Fischer, E.S., et al
    • Journal Title

      Cell

      Volume: 147 Issue: 5 Pages: 1024-1039

    • DOI

      10.1016/j.cell.2011.10.035

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NBS1 recruits RAD18 via aRAD6-like domain and regulates Polη-dependent translesion DNA synthesis2011

    • Author(s)
      Yanagihara H, Kobayashi J, Tateishi S, Kato A, Matsuura S, Tauchi H, Yamada K, Takezawa J, Sugasawa K, Masutani C, Hanaoka F, Weemaes CM, Mori T, Zou L, Komatsu K.
    • Journal Title

      Mol Cell

      Volume: 43 Issue: 5 Pages: 788-797

    • DOI

      10.1016/j.molcel.2011.07.026

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular chaperone Hsp90 regulates REV1-mediated mutagenesis.2011

    • Author(s)
      Pozo FM
    • Journal Title

      Mol Cell Biol

      Volume: 31 Issue: 16 Pages: 3396-3409

    • DOI

      10.1128/mcb.05117-11

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of a Y-family DNA polymerase η from the eukaryotic thermophile Avinella pompejana2010

    • Author(s)
      Kashiwagi, S., et al
    • Journal Title

      J.Nucleic Acids

      Volume: Sep 20 Pages: 701472-701472

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stimulation of DNA glycosylase activity by XPC protein complex : roles of protein-protein interactions2010

    • Author(s)
      Shimizu, Y., et al
    • Journal Title

      J.Nucleic Acids

      Volume: Jul 25 Pages: 805698-805698

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure and mutagenesis studies of the C-terminal region of licensing factor Cdt1 enable the identification of key residues for binding to replicative helicase Mcm proteins2010

    • Author(s)
      Jee, J., et al
    • Journal Title

      J.Biol.Chem.

      Volume: 285 Pages: 15931-15940

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Functional roles of TLS polymerases in mouse skin upon UV irradiation.2015

    • Author(s)
      Hanaoka F
    • Organizer
      Gordon Research Conference on Mammalian DNA Repair
    • Place of Presentation
      Ventura, California, USA
    • Year and Date
      2015-02-08 – 2015-02-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Roles of mammalian DNA polymerases eta and iota in UV-induced mutagenesis.2014

    • Author(s)
      Hanaoka F, Sakurai Y, Yokoi M
    • Organizer
      The 9th 3R Symposium
    • Place of Presentation
      御殿場
    • Year and Date
      2014-11-17 – 2014-11-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Roles of DNA polymerases eta and iota in UV-induced mutagenesis.2014

    • Author(s)
      Sakurai Y, Yokoi M, Hanaoka F
    • Organizer
      5th US-Japan DNA Repair Meeting
    • Place of Presentation
      鳴門、徳島
    • Year and Date
      2014-10-28 – 2014-10-31
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Roles of translesion synthesis polymerases eta and iota in UV-induced mutagenesis in mice2014

    • Author(s)
      Sakurai Y, Yokoi M, Murakumo Y, Hanaoka F
    • Organizer
      ZING Conferences DNA Polymerases: Biology, Diseases and Biomedical Applications Conference 2014
    • Place of Presentation
      Cambridge, UK
    • Year and Date
      2014-08-31 – 2014-09-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 損傷トレランス研究の40年:SOS応答から損傷乗り越えポリメラーゼへ2014

    • Author(s)
      花岡文雄
    • Organizer
      第36回日本光医学・光生物学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-07-25 – 2014-07-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 損傷トレランスと突然変異生成に働く損傷乗り越え合成ポリメラーゼ2014

    • Author(s)
      花岡文雄
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Year and Date
      2014-03-28 – 2014-03-30
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Defective translesion DNA synthesis and links to human disease.2014

    • Author(s)
      Hanaoka F
    • Organizer
      International Symposium on Xeroderma Pigmentosum and Related Diseases: Disorders of DNA Damage Response -Bench to Bedside-
    • Place of Presentation
      神戸
    • Year and Date
      2014-03-05 – 2014-03-07
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Role of DNA polymerase eta in somatic hypermutation.2013

    • Author(s)
      Hanaoka F
    • Organizer
      3rd France-Japan Cancer Meeting
    • Place of Presentation
      Toulouse, France
    • Year and Date
      2013-11-20 – 2013-11-23
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] がんとは何か?ーその発生のメカニズムを探るー2013

    • Author(s)
      花岡文雄
    • Organizer
      読売サイエンスフォーラム
    • Place of Presentation
      学習院大学
    • Year and Date
      2013-07-27
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Structure and function of mammalian DNA polymerase eta with special reference on translesion synthesis and somatic hypermutation.2013

    • Author(s)
      Hanaoka F
    • Organizer
      Seminar at Graduate School of Medicine, Kyoto University
    • Place of Presentation
      京都大学医学部
    • Year and Date
      2013-05-27
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Involvement of DNA polymerase eta-REV1 interaction in a part of error-prone translesion DNA synthesis.2012

    • Author(s)
      Hanaoka F
    • Organizer
      The 4th U.S.-Japan DNA Repair Meeting
    • Place of Presentation
      Virginia, USA
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Functional roles of mammalian DNA polymerase eta, the product of the XP-V responsible gene.2012

    • Author(s)
      Hanaoka F
    • Organizer
      The 3rd Erling Seeberg Symposium on DNA Repair
    • Place of Presentation
      Trondheim and Orland, Norway
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Alternative translesion synthesis pathway via interaction between stalled DNA polymerase eta and REV12012

    • Author(s)
      Hanaoka F
    • Organizer
      The 8th 3R Symposium together with National Institute of Genetics “2012 International Symposium”: “Molecular Mechanisms and Pathology of the 3R”
    • Place of Presentation
      淡路市、兵庫
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Functional roles of mammalian DNA polymerase eta2012

    • Author(s)
      Hanaoka F
    • Organizer
      2nd Japanese-Frence Cancer Workshop
    • Place of Presentation
      鳴門市、徳島
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] DNA修復と疾患:色素性乾皮症を中心に2011

    • Author(s)
      花岡文雄
    • Organizer
      第28回日本医学会総会
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] Biochemical properties and structure of human DNA polymerase η.2011

    • Author(s)
      Hanaoka, F.
    • Organizer
      6th UK-Japan Cell Cycle Workshop
    • Place of Presentation
      Lake Windermere, UK
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] DNA修復研究における生化学的アプローチ2011

    • Author(s)
      花岡文雄
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会議場
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] Biochemical properties and structure of human DNA polymerase &eta, xeroderma pigmentosum variant-responsible gene product2011

    • Author(s)
      Hanaoka, F.
    • Organizer
      GDRI France Japan Conference
    • Place of Presentation
      Montpellier, France
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] ヒト細胞の損傷乗り越えDNA複製の制御機構の解析2010

    • Author(s)
      益谷央豪, など
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会ワークショップ
    • Place of Presentation
      神戸ポートアイランド(招待講演)
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] DNAポリメラーゼ・イータ ―その構造と多彩な機能―

    • Author(s)
      花岡文雄
    • Organizer
      新学術領域研究「遺伝情報場」公開シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Remarks] 学習院大学 花岡研究室

    • URL

      http://www-cc.gakushuin.ac.jp/~20080213/

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
  • [Remarks]

    • URL

      http://www-cc.gakushuin.ac.jp/~20080213/

    • Related Report
      2010 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

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