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Functional analysis of cellular tolerance to chronic genotoxic stress in Saccharomyces cerevisiae

Research Project

Project/Area Number 23247002
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Genetics/Genome dynamics
Research InstitutionGakushuin University

Principal Investigator

Hishida Takashi  学習院大学, 理学部, 教授 (60335388)

Project Period (FY) 2011-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥42,510,000 (Direct Cost: ¥32,700,000、Indirect Cost: ¥9,810,000)
Fiscal Year 2014: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2013: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2012: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2011: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
KeywordsDNA損傷 / 出芽酵母 / DNA損傷トレランス / DNA修復 / DNA相同組換え / Mgs1 / DNA複製 / ゲノム安定性 / クロマチン
Outline of Final Research Achievements

DNA damage tolerance (DDT) provides a mechanism to tolerate chronic genotoxic stress during replication, allowing the lesions to be repaired after replication, thus reducing the overall risk of genome instability. The post-translational modification of PCNA, proliferating cell nuclear antigen, by ubiquitination plays an important role in coordinating the process of DNA damage tolerance. Here we examined the effects of mutations in the Mgs1 ATPase, UBZ and C-terminal domains on DNA damage tolerance. The results demonstrate that the UBZ domain negatively regulates the DDT pathway, whereas the C-terminal domain stimulates the homologous recombination pathway, implicating a role for Mgs1 in the regulation of both pathways. We also found an increasing number of metabolic compounds, such as trehalose and reactive oxygen species, linked with the maintenance of genome integrity. These observations underscore the importance of metabolic functions on replication stress tolerance.

Report

(5 results)
  • 2015 Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (30 results)

All 2015 2014 2013 2012 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (25 results) (of which Invited: 2 results) Book (2 results)

  • [Journal Article] RecA protein recruits structural maintenance of chromosomes (SMC)-like RecN protein to DNA double-strand breaks2013

    • Author(s)
      Keyamura K, Sakaguchi C, Kubota Y, Niki H, Hishida T.
    • Journal Title

      J Biol Chem.

      Volume: 288(41) Issue: 41 Pages: 29229-29237

    • DOI

      10.1074/jbc.m113.485474

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Chronic low-dose ultraviolet induced mutagenesis in nucleotide excision repair-deficient cells2012

    • Author(s)
      Haruta, N., et. al.
    • Journal Title

      Nucleic Acids Res.

      Volume: 40 Pages: 8406-8415

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] En bloc transfer of polyubiquitin chains to PCNA in vitro is mediated by two different human E2-E3 pairs2012

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

      Nucleic Acids Res.

      Volume: 40 Pages: 10394-10407

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 相同染色体間の組換え制御メカニズムの解析2015

    • Author(s)
      毛谷村賢司、菱田卓
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] A genetic screen for genes that suppress the temperature sensitivity of mgs1-18 rad18∆ cells in Saccharomyces cerevisiae2015

    • Author(s)
      Ishige, D., Keyamura, K., Hasegawa, Y., Iwasaki, H., and Hishida, T.
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] 出芽酵母Srs2ヘリカーゼとMus81-Mms4ヌクレアーゼによる相同染色体間の組換え制御機構2015

    • Author(s)
      毛谷村賢司、菱田卓
    • Organizer
      第23回DNA複製・組換え・修復ワークショップ
    • Place of Presentation
      静岡
    • Year and Date
      2015-10-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] 出芽酵母における複製ストレス応答に関わる新たな因子の探索2015

    • Author(s)
      石毛大輔、毛谷村賢司、長谷川ゆき、岩﨑博史、菱田卓
    • Organizer
      第23回DNA複製・組換え・修復ワークショップ
    • Place of Presentation
      静岡
    • Year and Date
      2015-10-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] 複製ストレス応答における出芽酵母Mgs1の役割2015

    • Author(s)
      長谷川ゆき、毛谷村賢司、重森悠、菱田卓
    • Organizer
      第23回DNA複製・組換え・修復ワークショップ
    • Place of Presentation
      静岡
    • Year and Date
      2015-10-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] 出芽酵母における複製ストレス応答に関わる新たな因子の探索2015

    • Author(s)
      石毛大輔、毛谷村賢司、長谷川ゆき、岩﨑博史、菱田卓
    • Organizer
      第87回日本遺伝学会
    • Place of Presentation
      東北大
    • Year and Date
      2015-09-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 慢性的な低線量率紫外線照射下における出芽酵母NER欠損株の動態解析2015

    • Author(s)
      塩入拓馬、毛谷村賢司、田中修平、菱田卓
    • Organizer
      第87回日本遺伝学会
    • Place of Presentation
      東北大
    • Year and Date
      2015-09-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 二本鎖DNAの切断修復に関与するRecNの機能解析2015

    • Author(s)
      毛谷村賢司、戸羽あす美、仁木宏典、菱田卓
    • Organizer
      第12回21世紀大腸菌研究会
    • Place of Presentation
      滋賀
    • Year and Date
      2015-06-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] 相同染色体間の組換え制御機構における出芽酵母Srs2の役割2014

    • Author(s)
      毛谷村賢司、菱田卓
    • Organizer
      第32回染色体ワークショップ・第13回核ダイナミクス研究会
    • Place of Presentation
      広島大
    • Year and Date
      2014-12-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] 出芽酵母Mgs1タンパク質の機能ドメインの解析2014

    • Author(s)
      重森悠、毛谷村賢司、菱田卓
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] DNA損傷ストレス応答に影響を及ぼすヒストン変異体の解析2014

    • Author(s)
      吉田麻美、毛谷村賢司、菱田卓
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Roles of the Saccharomyces cerevisiae Srs2 helicase in inter-homologue recombination repair2014

    • Author(s)
      毛谷村賢司、新井康太、菱田卓
    • Organizer
      第9回3Rシンポジウム
    • Place of Presentation
      静岡
    • Year and Date
      2014-11-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] 菱田卓2014

    • Author(s)
      慢性的な紫外線損傷ストレスに対する耐性獲得に関与するヌクレオソーム構造
    • Organizer
      第57回日本放射線影響学会
    • Place of Presentation
      鹿児島
    • Year and Date
      2014-10-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] DNA損傷ストレス応答に関与するヒストン変異体の網羅的解析2014

    • Author(s)
      吉田麻美、毛谷村賢司、菱田卓
    • Organizer
      第86回日本遺伝学会
    • Place of Presentation
      滋賀
    • Year and Date
      2014-09-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] DNA二本鎖切断修復に関与するRecNのDNA相互作用メカニズムの解析2014

    • Author(s)
      毛谷村賢司、金子佳樹、仁木宏典、菱田卓
    • Organizer
      第11回21世紀大腸菌研究会
    • Place of Presentation
      盛岡
    • Year and Date
      2014-06-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] SMCファミリータンパク質RecNのDNA二重鎖切断修復における役割2013

    • Author(s)
      毛谷村賢司、久保田佳乃、小林万希子、金子佳樹、仁木宏典、菱田卓
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-03 – 2013-12-06
    • Related Report
      2013 Annual Research Report
  • [Presentation] 出芽酵母を用いたジーンターゲティングに関与する新規因子の同定2013

    • Author(s)
      櫻本健郎、毛谷村賢司、菱田卓
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-03 – 2013-12-06
    • Related Report
      2013 Annual Research Report
  • [Presentation] 相同染色体間の組換えにおける出芽酵母 Srs2 へリカーゼの役割2013

    • Author(s)
      毛谷村賢司、新井康太、菱田卓
    • Organizer
      第22回DNA複製、組換え、修復ワークショップ
    • Place of Presentation
      仙台・秋保温泉
    • Year and Date
      2013-11-20 – 2013-11-22
    • Related Report
      2013 Annual Research Report
  • [Presentation] 出芽酵母を用いたジーンターゲティングに関する新規遺伝子の探索2013

    • Author(s)
      櫻本健郎、毛谷村賢司、菱田卓
    • Organizer
      第22回DNA複製、組換え、修復ワークショップ
    • Place of Presentation
      仙台・秋保温泉
    • Year and Date
      2013-11-20 – 2013-11-22
    • Related Report
      2013 Annual Research Report
  • [Presentation] 相同染色体間のDNA相同組換え制御メカニズムの解析2013

    • Author(s)
      毛谷村賢司、新井康太、菱田卓
    • Organizer
      第85回日本遺伝学会
    • Place of Presentation
      慶応大学
    • Year and Date
      2013-09-19 – 2013-09-21
    • Related Report
      2013 Annual Research Report
  • [Presentation] DNA二重鎖切断修復に関与するSMCファミリータンパク質RecNの機能解析2013

    • Author(s)
      毛谷村賢司、久保田佳乃、仁木宏典、菱田卓
    • Organizer
      第10回21世紀大腸菌研究会
    • Place of Presentation
      伊豆・修善寺
    • Year and Date
      2013-06-20 – 2013-06-21
    • Related Report
      2013 Annual Research Report
  • [Presentation] 慢性的な紫外線照射による突然変異の誘起メカニズム2012

    • Author(s)
      菱田卓
    • Organizer
      放射線影響学会第55回大会
    • Place of Presentation
      仙台
    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Invited
  • [Presentation] 相同染色体間の組換え制御機構の解析2012

    • Author(s)
      菱田卓
    • Organizer
      第84回日本遺伝学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
  • [Presentation] Srs2による相同染色体間の組換え制御機構2012

    • Author(s)
      菱田卓
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
  • [Presentation] DNA二重鎖切断修復に関与するRecNの機能解析

    • Author(s)
      菱田卓
    • Organizer
      第9回21世紀大腸菌研究会
    • Place of Presentation
      滋賀
    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
  • [Book] ゲノムを司るインターメア:非コードDNA領域のDNA損傷応答2015

    • Author(s)
      菱田 卓
    • Publisher
      化学同人
    • Related Report
      2014 Annual Research Report
  • [Book] パリティ2015

    • Author(s)
      菱田 卓
    • Publisher
      丸善出版
    • Related Report
      2014 Annual Research Report

URL: 

Published: 2011-06-18   Modified: 2019-07-29  

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