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Establishment of Novel Bioassays for in vivo Genotoxicity Prediction and Mechanism Characterization

Research Project

Project/Area Number 16H06306
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Risk sciences of radiation and chemicals
Research InstitutionKyoto University

Principal Investigator

武田 俊一  京都大学, 医学研究科, 教授 (60188191)

Co-Investigator(Kenkyū-buntansha) 廣田 耕志  東京都立大学, 理学研究科, 教授 (00342840)
笹沼 博之  京都大学, 医学研究科, 准教授 (00531691)
安井 学  国立医薬品食品衛生研究所, 変異遺伝部, 室長 (50435707)
Brown John  京都大学, 医学研究科, 講師 (90583188)
津田 雅貴  京都大学, 医学研究科, 特定助教 (00734104)
Project Period (FY) 2016-05-31 – 2021-03-31
Project Status Granted (Fiscal Year 2020)
Budget Amount *help
¥183,170,000 (Direct Cost: ¥140,900,000、Indirect Cost: ¥42,270,000)
Fiscal Year 2020: ¥35,100,000 (Direct Cost: ¥27,000,000、Indirect Cost: ¥8,100,000)
Fiscal Year 2019: ¥38,090,000 (Direct Cost: ¥29,300,000、Indirect Cost: ¥8,790,000)
Fiscal Year 2018: ¥33,020,000 (Direct Cost: ¥25,400,000、Indirect Cost: ¥7,620,000)
Fiscal Year 2017: ¥32,110,000 (Direct Cost: ¥24,700,000、Indirect Cost: ¥7,410,000)
Fiscal Year 2016: ¥44,850,000 (Direct Cost: ¥34,500,000、Indirect Cost: ¥10,350,000)
Keywordsトキシコロジー / 遺伝毒物学 / 発がん物質 / 変異原 / 抗がん治療薬 / 人体有害物質 / TK6細胞 / ケモインフォマティクス
Outline of Annual Research Achievements

本研究の第一の目的は、化学物質審査規制法(化審法)で規定された変異原性検出試験の感度を改善し、世界標準の変異原性検出試験法を樹立することにある。感度改善は、ヒトTK6細胞(OECDガイドラインと化審法で推奨)由来の、DNA修復酵素欠損株を作製・利用して達成する。第二の研究目的は、変異原性の作用機序を迅速に分類分けする手法を創ることにある。分類分けは、in silico の変異原性検出手法の開発に貢献する。第三に、in silico の変異原性検出手法の手法を開発する。最後に、我々がDNA修復酵素欠損株を使って発見した、DNA毒性・変異原性の新たな作用機序を解明する。
我々は、TK変異試験(化審法に規定)の感度を5倍上られるDNA修復酵素欠損TK6株を創った(Ibrahim MA et al., 2020)。感度を上昇させることができるTK6株を創るだけでなく、化審法に規定された手法を使い、作用機序を迅速に分類分けできるTK6株も創った(TK6コンソーシアムのwebサイトに公開)。in silico の変異原性検出手法の開発した(Polash AH. Et al., 2019; Nakano T. et al., 2020)。DNA毒性・変異原性の新たな作用機序を解明することについては、以下の成果があった。リボヌクレオチド(RNA合成の基質)が間違ってDNAに取込まれた時に、ヌクレオチド除去修復がそのリボヌクレオチドをDNAから除去することを発見した(Sassa A et al., 2019)。電離放射線照射はゲノムを切断しかつその切断端には多様な化学修飾ができる。この化学修飾を除去する酵素群を同定した(Akagawa R. et al., 2020)。また男性ホルモンの前立腺に対する強いDNA毒性を発見した(Mahmud RA. et al., 2020)。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

4つの理由を以下に説明する。
1) 我々は、xpa/xrcc1 二重破壊TK6株を創り(Ibrahim MA et al., 2020)、そして菌を使うエイムス試験では陽性を示すが、哺乳類細胞を用いる変異原性検出試験では陰性を示す、従来、変異原性偽陽性と一応説明されてきた化学物質の変異原性を証明した。本研究の意義は以下の通りである。行政や化学産業のニーズは、AIにより新規化合物の化学構造から変異原性を予測することである。この予測(QSARと呼ばれる)実現には、質の高い学習データが必要である。AIの学習データには本間正充博士(分担研究者の安井博士の直接の上司)が収集したエイムス試験の結果(~20,000化合物)が全世界で使われている。二重破壊TK6株を使ったTK試験により「従来、変異原性偽陽性と一応説明されてきた化学物質」が変異原性陽性であることが証明できた。この成果は、全世界で使われるQSARの性能向上に貢献する。
2) in silico の変異原性検出手法について2報論文発表した。
3) DNA二重鎖切断は、放射線被曝で生じ、発がん性が非常に強い。我々は、DNA切断が自然発生する機序を見つけた。このDNA切断を再結合するDNA修復酵素の欠損株を作った。この欠損株を使い、生理濃度の女性ホルモンや男性ホルモン、環境ホルモン(例、ビスフェノール)が高いDNA切断活性を持つことを発見した。
4) 紫外線やシスプラチン(抗癌剤)で生じる損傷は、従来、ヌクレオチド除去修復(NER)のみが修復すると考えされてきた。そしてNERはミトコンドリアで機能しないが故に、紫外線損傷やシスプラチン損傷はミトコンドリアDNAから除去されないと考えされてきた。我々は、この定説を覆し、まず染色体DNAの紫外線損傷がNER以外の経路によって修復されることを論文発表した(2020年4月にPNAS USAに採択)。

Strategy for Future Research Activity

(1)従来、変異原性偽陽性と一応説明されてきた化合物(オーラミンとパラフェニレンジアミン)の、ヒト細胞における変異原性を証明し論文発表する。
(2)我々が発見した、ミトコンドリアDNA(mtDNA)に生じたUV損傷を修復する経路を論文発表する。
(3)我々が発見した、染色体DNAとmtDNAに生じたシスプラチン損傷を修復する経路について論文発表する。mtDNAの修復には、ミトコンドリア特異的DNA Topoisomerase I (TOP1MT) が関与していた。既知のmtDNA修復因子はすべて細胞核でも機能しているが、TOP1MTはmtDNAでのみ機能する、唯一の修復因子である。一方、NERは細胞核でのみ機能する。TOP1MT欠損マウスとNER欠損マウスを既に取得済みである。これらの欠損マウスの表現型をシスプラチン曝露後に比較することによって、mtDNAのみに損傷が蓄積する影響を、染色体DNAのみに損傷が蓄積する影響から区別しながら、解析できる動物実験系を世界で初めて樹立できる。この成果を論文発表する。予備実験から、TOP1MTが欠損するとシスプラチンの急性腎毒性が強く顕れることを既に確認した。
(4)男性ホルモンの変異原性を解析する動物実験系を樹立した(Mahmud RA. et al., 2020)。この研究を発展させ、この変異原性による発癌機序を解析する動物実験系を樹立し、性ホルモンによる乳腺、卵巣、前立腺の発癌機序を解明する。実験手法は、変異原性を高めるATM酵素阻害剤と性ホルモンとを毎日30日間腹腔注射することである。そして30日後に乳腺、卵巣、前立腺において癌を多発させることを目指す。
(5)様々な環境ホルモンの変異原性をハイスループットに検出する共同研究を、米国NIHの研究者(Dr. Xia Menghang)と実施している。この研究成果を発表する。

Report

(6 results)
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Abstract ( PDF )   Comments on the Screening Results ( PDF )   Annual Research Report

Research Products

(166 results)

All 2020 2019 2018 2017 2016 Other

All Int'l Joint Research Journal Article Presentation Book Remarks

  • [Int'l Joint Research] National Institutes of Health/Memorial Sloan Kettering Cancer Center/Brandeis University(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Sussex(英国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] IFOM研究所(イタリア)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] 上海交通大学(中国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] スイス連邦チューリッヒ工科大学(スイス)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] National Institutes of Health/Memorial Sloan-Kettering Cancer Center(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Laboratory of Molecular Biology/University of Sussex(英国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] DNA Damage Tolerance CNRS/Universite Pierre et Marie Curie(フランス)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] IFOM(イタリア)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] IFOM(イタリア)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] マサチューセッツ工科大学/National Institutes of Health/スローンケタリング癌研究所(アメリカ)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] スイス連邦工科大学チューリッヒ校(スイス)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] National Intsitutes of Health/ボストン大学/ノースカロライナ大学(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] ケンブリッジ大学内のMRC 分子生物学研究所/サセックス大学/レスター大学(英国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] UBC13-mediated ubiquitin signaling promotes removal of blocking adducts from DNA double-strand breaks.2020

    • Author(s)
      Akagawa R, Trinh TH, Saha LK, Tsuda M, Hirota K, Yamada S, Shibata A, Kanemaki MT, Nakada S, Takeda S, Sasanuma H
    • Journal Title

      iScience

      Volume: 23 Pages: 101027-101027

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TDP2 suppresses genomic instability induced by androgens in the epithelial cells of prostate glands.2020

    • Author(s)
      Mahmud RA, Ishii K, Lozano BC, Sainz DI, Toi M, Akamatsu S, Fukumoto M, Watanabe M, Takeda S, Ledesma FC, Sasanuma H
    • Journal Title

      Genes Cells

      Volume: in press

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Enhancing the sensitivity of the thymidine kinase assay by using DNA repair-deficient human TK6 cells2020

    • Author(s)
      Ibrahim MA, Yasui M, Saha LK, Sasanuma H, Honma M, Takeda S
    • Journal Title

      Environmental and Molecular Mutagenesis

      Volume: in press

    • DOI

      10.1002/em.22371

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prediction of Compound Cytotoxicity Based on Compound Structures and Cell Line Molecular Characteristics2020

    • Author(s)
      Nakano T, Brown JB
    • Journal Title

      J. Comput. Aided Chem.

      Volume: 21 Issue: 0 Pages: 1-1

    • DOI

      10.2751/jcac.21.1

    • ISSN
      1345-8647
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Type II DNA Topoisomerases Cause Spontaneous Double-Strand Breaks in Genomic DNA.2019

    • Author(s)
      Morimoto S, Tsuda M, Bunch H, Sasanuma H, Austin C, Takeda S
    • Journal Title

      Genes

      Volume: 10 Pages: 868-868

    • DOI

      10.3390/genes10110868

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Applicability Domain of Active Learning in Chemical Probe Identification: Convergence in Learning from Non-Specific Compounds and Decision Rule Clarification.2019

    • Author(s)
      Polash AH, Nakano T, Takeda S, Brown JB
    • Journal Title

      Molecules

      Volume: 24 Pages: 2716-2716

    • DOI

      10.3390/molecules24152716

    • NAID

      120006712779

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative study of cytotoxic effects induced by environmental genotoxins using XPC- and CSB-deficient human lymphoblastoid TK6 cells.2019

    • Author(s)
      Sassa Akira、Fukuda Takayuki、Ukai Akiko、Nakamura Maki、Takabe Michihito、Takamura-Enya Takeji、Honma Masamitsu、Yasui Manabu
    • Journal Title

      Genes Environ.

      Volume: 41 Pages: 15-15

    • DOI

      10.1186/s41021-019-0130-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PDIP38/PolDIP2 controls the DNA damage tolerance pathways by increasing the relative usage of translesion DNA synthesis over template switching2019

    • Author(s)
      Tsuda M, Ogawa S, Ooka M, Kobayashi K, Hirota K, Wakasugi M, Matsunaga T, Sakuma T, Yamamoto T, Chikuma S, Sasanuma H, Debatisse M, Doherty AJ, Fuchs RP, Takeda S
    • Journal Title

      PloS one

      Volume: 14

    • DOI

      10.1371/journal.pone.0213383

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation.2019

    • Author(s)
      Zong D, Adam S, Wang Y, Sasanuma H, Callen E, Murga M, Day A, Kruhlak MJ, Wong N, Munro M, Ray Chaudhuri A, Karim B, Xia B, Takeda S, Johnson N, Durocher D, Nussenzweig A
    • Journal Title

      Mol Cell

      Volume: 73 Pages: 1267-1281

    • DOI

      10.1016/j.molcel.2018.12.010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] lncRNA transcriptional initiation induces chromatin remodeling within a limited range in the fission yeast fbp1 promoter2019

    • Author(s)
      Senmatsu S, Asada R, Abe T, Hoffman CS, Ohta K, Hirota K
    • Journal Title

      Scientific Reports

      Volume: 9 Pages: 299-299

    • DOI

      10.1038/s41598-018-36049-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Landscape of the complete RNA chemical modifications in the human 80S ribosome2019

    • Author(s)
      Taoka M, Nobe Y, Yamaki Y, Sato K, Ishikawa H, Izumikawa K, Yamauchi Y, Hirota K, Nakayama H, Takahashi N, Isobe T.
    • Journal Title

      Nucleic Acids Research

      Volume: 46 Pages: 9289-9298

    • DOI

      10.1093/nar/gky811

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Current perspectives on mechanisms of ribonucleotide incorporation and processing in mammalian DNA.2019

    • Author(s)
      Sassa Akira、Yasui Manabu、Honma Masamitsu
    • Journal Title

      Genes Environ.

      Volume: 41 Pages: 3-3

    • DOI

      10.1186/s41021-019-0118-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Systematic approaches to build predictive models for rat oral toxicity.2019

    • Author(s)
      Polash AH, Nakano T, Takeda S, *Brown JB
    • Journal Title

      CICSJ Bulletin

      Volume: 37 Pages: 12-21

    • NAID

      130007639336

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SUMOylation of PCNA by PIAS1 and PIAS4 promotes template switch in the chicken and human B cell lines.2018

    • Author(s)
      Mohiuddin Mohiuddin、Evans Terry John、Rahman Md Maminur、Keka Islam Shamima、Tsuda Masataka、Sasanuma Hiroyuki、Takeda Shunichi
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 115 Pages: 12793-12798

    • DOI

      10.1073/pnas.1716349115

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] BRCA1 ensures genome integrity by eliminating estrogen-induced pathological topoisomerase II-DNA complexes.2018

    • Author(s)
      Sasanuma Hiroyuki、Tsuda Masataka、Morimoto Suguru、Saha Liton Kumar、Rahman Md Maminur、Kiyooka Yusuke、Fujiike Haruna、Cherniack Andrew D.、Itou Junji、Callen Moreu Elsa、Toi Masakazu、Nakada Shinichiro、Tanaka Hisashi、Tsutsui Ken、Yamada Shintaro、Nussenzweig Andre、Takeda Shunichi
    • Journal Title

      Proc Natl Acad Sci USA.

      Volume: 115

    • DOI

      10.1073/pnas.1803177115

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differential micronucleus frequency in isogenic human cells deficient in DNA repair pathways is a valuable indicator for evaluating genotoxic agents and their genotoxic mechanisms.2018

    • Author(s)
      Saha LK, Kim S, Kang H, Akter S, Choi K, Sakuma T, Yamamoto T, Sasanuma H, Hirota K, Nakamura J, Honma M, Takeda S
    • Journal Title

      Environ Mol Mutagen

      Volume: 59 Pages: 529-538

    • DOI

      10.1002/em.22201

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] DNA Damage Tolerance Mechanisms Revealed from the Analysis of Immunoglobulin V Gene Diversification in Avian DT40 Cells.2018

    • Author(s)
      Abe T, Branzei D, Hirota K
    • Journal Title

      Genes (Basel)

      Volume: 9

    • DOI

      10.3390/genes9120614

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] AND-1 fork protection function prevents fork resection and is essential for proliferation.2018

    • Author(s)
      Abe T, Kawasumi R, Giannattasio M, Dusi S, Yoshimoto Y, Miyata K, Umemura K, Hirota K, Branzei D
    • Journal Title

      Nat Commun

      Volume: 9 Pages: 3091-3091

    • DOI

      10.1038/s41467-018-05586-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Warsaw breakage syndrome DDX11 helicase acts jointly with RAD17 in the repair of bulky lesions and replication through abasic sites.2018

    • Author(s)
      Abe T, Ooka M, Kawasumi R, Miyata K, Takata M, Hirota K, Branzei D
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 115 Pages: 8412-8417

    • DOI

      10.1073/pnas.1803110115

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SPARTAN promotes genetic diversification of the immunoglobulin-variable gene locus in avian DT40 cells.2018

    • Author(s)
      Nakazato A, Kajita K, Ooka M, Akagawa R, Abe T, Takeda S, Branzei D, Hirota K
    • Journal Title

      DNA Repair (Amst)

      Volume: 68 Pages: 50-57

    • DOI

      10.1016/j.dnarep.2018.06.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Histone Chaperone Asf1 Is Required for the Establishment of Repressive Chromatin in Schizosaccharomyces pombe fbp1 Gene Repression2018

    • Author(s)
      Umeda M, Tsunekawa C, Senmatsu S, Asada R, Abe T, Ohta K, Hoffman CS, Hirota K
    • Journal Title

      Molecular and Cellular Biology

      Volume: 38

    • DOI

      10.1128/mcb.00194-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adaptive mining and model building of medicinal chemistry data with a multi-metric perspective2018

    • Author(s)
      Brown JB
    • Journal Title

      Future Medicinal Chemistry

      Volume: 10 Pages: 1885-1887

    • DOI

      10.4155/fmc-2018-0188

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chromatin remodeler ALC1 prevents replication-fork collapse by slowing fork progression.2018

    • Author(s)
      Ooka M, Abe T, Cho K, Koike K, Takeda S, Hirota K.
    • Journal Title

      PLoS One

      Volume: 13(2)

    • DOI

      10.1371/journal.pone.0192421

    • NAID

      120006457113

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemogenomic active learning's domain of applicability on small, sparse qHTS matrices: a study using CYP450 and nuclear hormone receptor families.2018

    • Author(s)
      Rakers Christin、Najnin Rifat Ara、Polash Ahsan Habib、Takeda Shunichi、Brown J.B.
    • Journal Title

      ChemMedChem.

      Volume: 13 Pages: 511-521

    • DOI

      10.1002/cmdc.201700677

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Disruption of Hif-1α enhances cytotoxic effects of metformin in murine squamous cell carcinoma2018

    • Author(s)
      Sanada Y, Sasanuma H, Takeda S, Tano K, Masunaga S.
    • Journal Title

      International Journal of Radiation Biology

      Volume: 94 Pages: 88-96

    • DOI

      10.1080/09553002.2018.1409443

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Classifiers and their metrics quantified.2018

    • Author(s)
      Brown J. B.
    • Journal Title

      Molecular Informatics

      Volume: 37 Pages: 1700127-1700127

    • DOI

      10.1002/minf.201700127

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interplay between chromatin modulators and histone acetylation regulates the formation of accessible chromatin in the upstream regulatory region of fission yeast <i>fbp1</i>2018

    • Author(s)
      Akira Adachi、?Satoshi Senmatsu、?Ryuta Asada、?Takuya Abe、?Charles S. Hoffman、?Kunihiro Ohta、?Kouji Hirota
    • Journal Title

      Genes & Genetic Systems

      Volume: 92 Issue: 6 Pages: 267-276

    • DOI

      10.1266/ggs.17-00018

    • NAID

      130006731266

    • ISSN
      1341-7568, 1880-5779
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ALC1/CHD1L, a chromatin-remodeling enzyme, is required for efficient base excision repair2017

    • Author(s)
      Tsuda M, Cho K, Ooka M, Shimizu N, Watanabe R, Yasui A, Nakazawa Y, Ogi T, Harada H, Agama K, Nakamura J, Asada R, Fujiike H, Sakuma T, Yamamoto T, Murai J, Hiraoka M, Koike K, Pommier Y, Takeda S, Hirota K.
    • Journal Title

      PLOS ONE

      Volume: 12

    • DOI

      10.1371/journal.pone.0188320

    • NAID

      120006533284

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Complementation of aprataxin deficiency by base excision repair enzymes in mitochondrial extracts.2017

    • Author(s)
      Caglayan M, Prasad R, Krasich R, Longley MJ, Kadoda K, Tsuda M, Sasanuma H, Takeda S, Tano K, Copeland WC and Wilson SH
    • Journal Title

      Nucleic Acids Res.

      Volume: 45 Pages: 10079-10088

    • DOI

      10.1093/nar/gkx654

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Selective cytotoxicity of the anti-diabetic drug, metformin, in glucose-deprived chicken DT40 cells.2017

    • Author(s)
      Kadoda K, Moriwaki T, Tsuda M, Sasanuma H, Ishiai M, Takata M, Ide H, Masunaga S, Takeda S and Tano K
    • Journal Title

      PLoS One

      Volume: 12

    • DOI

      10.1371/journal.pone.0185141

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TDP1 is critical for the repair of DNA breaks induced by sapacitabine, a nucleoside also targeting ATM- and BRCA-deficient tumors.2017

    • Author(s)
      Abo MA, Sasanuma H, Liu X, Rajapakse VN, Huang SN, Kiselev E, Takeda S, Plunkett W, Pommier Y
    • Journal Title

      Mol Cancer Ther.

      Volume: 16 Pages: 2543-2551

    • DOI

      10.1158/1535-7163.mct-17-0110

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] SEL1L-dependent Substrates Require Derlin2/3 and Herp1/2 for Endoplasmic Reticulum-associated Degradation2017

    • Author(s)
      Takehiro Sugimoto, Satoshi Ninagawa, Shimpei Yamano, Tokiro Ishikawa, Tetsuya Okada, Shunichi Takeda, Kazutoshi Mori
    • Journal Title

      Cell Struct. Funct.

      Volume: 42-2 Issue: 2 Pages: 81-94

    • DOI

      10.1247/csf.17007

    • NAID

      130005708193

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple repair pathways mediate cellular tolerance to resveratrol-induced DNA damage.2017

    • Author(s)
      Liu Y, Wu X, Hu X, Chen Z, Liu H, Takeda S, Qing Y
    • Journal Title

      Toxicol In Vitro.

      Volume: 42 Pages: 130-138

    • DOI

      10.1016/j.tiv.2017.04.017

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The dominant role of proofreading exonuclease activety of replicative polymerase ε in cellular tolerance to cytarabine (Ara-C).2017

    • Author(s)
      Tsuda M, Terada K, Ooka M, Kobayashi K, Sasanuma H, Fujisawa R, Tsurimoto T, Yamamoto J, Iwai S, Kadoda K, Akagawa R, Huang SN, Pommier Y, Sale JE, Takeda S, Hirota K.
    • Journal Title

      Oncotarget.

      Volume: in press Pages: 33457-33474

    • DOI

      10.18632/oncotarget.16508

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Small Random Forest Models for Effective Chemogenomic Active Learning2017

    • Author(s)
      Rakers C, Reker D, Brown JB
    • Journal Title

      J. Comput. Aided Chem.

      Volume: 18 Issue: 0 Pages: 124-142

    • DOI

      10.2751/jcac.18.124

    • NAID

      130005877946

    • ISSN
      1345-8647
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ESCO1/2's roles in chromosome structure and interphase chromatin organization.2017

    • Author(s)
      Kawasumi R, Abe T, Arakawa H, Garre M, Hirota K, Branzei D.
    • Journal Title

      Genes Dev

      Volume: 31(21) Pages: 2136-2150

    • DOI

      10.1101/gad.306084.117

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Human CTF18-RFC clamp-loader complexed with non-synthesising DNA polymerase epsilon efficiently loads the PCNA sliding clamp.2017

    • Author(s)
      Fujisawa R, Ohashi E, Hirota K, Tsurimoto T.
    • Journal Title

      Nucleic Acids Res

      Volume: in press Pages: 4550-4563

    • DOI

      10.1093/nar/gkx096

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Recruitment and delivery of the fission yeast Rst2 transcription factor via a local genome structure counteracts repression by Tup1-family corepressors?2017

    • Author(s)
      Ryuta Asada?Miki Umeda?Akira Adachi?Satoshi Senmatsu?Takuya Abe?Hiroshi IwasakiKunihiro Ohta?Charles S. Hoffman?Kouji Hirota
    • Journal Title

      Nucleic Acids Res.

      Volume: 45 Pages: 9361-9371

    • DOI

      10.1093/nar/gkx555

    • NAID

      120006635260

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cytotoxicity of tirapazamine (3-amino-1, 2, 4-benzotriazine-1, 4-dioxide)-induced DNA damage in chicken DT40 cells2017

    • Author(s)
      Moriwaki T, Okamoto S, Sasanuma H, Nagasawa H, Takeda S, Masunaga S, Tano K
    • Journal Title

      Chem. Res. Toxicol.

      Volume: 30 Pages: 699-704

    • DOI

      10.1021/acs.chemrestox.6b00417

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Active learning for computational chemogenomics2017

    • Author(s)
      Reker D, Schneider P, Schneider G, Brown JB
    • Journal Title

      Future Medicinal Chemistry

      Volume: 9 Pages: 381-402

    • DOI

      10.4155/fmc-2016-0197

    • NAID

      120005997743

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Homologous recombination and translesion DNA synthesis play critical roles on tolerating DNA damage caused by trace levels of hexavalent chromium.2016

    • Author(s)
      Tian X, Patel K, Ridpath JR, Chen Y, Zhou YH, Neo D, Clement J, Takata M, Takeda S, Sale J, Wright FA, Swenberg JA, Nakamura J
    • Journal Title

      pLOSOne

      Volume: 11

    • DOI

      10.1371/journal.pone.0167503

    • NAID

      120005980904

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mre11 Is Essential for the Removal of Lethal Topoisomerase 2 Covalent Cleavage Complexes2016

    • Author(s)
      Hoa NN, Shimizu T, Zhou ZW, Wang ZQ, Deshpande RA, Paull TT, Akter S, Tsuda M, Furuta R, Tsusui K, Takeda S, Sasanuma H
    • Journal Title

      Molecular Cell

      Volume: 64 Pages: 580-592

    • DOI

      10.1016/j.molcel.2016.10.011

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Determination of genotoxic potential by comparison of structurally related azo dyes using DNA repair-deficient DT40 mutant panels.2016

    • Author(s)
      Ooka M, Kobayashi K, Abe T, Akiyama K, Hada M, Takeda S, Hirota K
    • Journal Title

      Chemosphere

      Volume: 164 Pages: 106-112

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A High-Throughput Screen Identifies 2,9-Diazaspiro[5.5]Undecanes as Inducers of the Endoplasmic Reticulum Stress Response with Cytotoxic Activity in 3D Glioma Cell Models.2016

    • Author(s)
      Martinez NJ, Rai G, Yasgar A, Lea WA, Sun H, Wang Y, Luci DK, Yang SM, Nishihara K, Takeda S, Sagor M, Earnshaw I, Okada T, Mori K, Wilson K, Riggins GJ, Xia M, Grimaldi M, Jadhav A, Maloney DJ, Simeonov A
    • Journal Title

      PLoS One

      Volume: 11

    • DOI

      10.1371/journal.pone.0161486

    • NAID

      120005997751

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Poor recognition of O6-isopropyl dG by MGMT triggers double strand break-mediated cell death and micronucleus induction in FANC-deficient cells2016

    • Author(s)
      Hashimoto K, Sharma V, Sasanuma H, Tian X, Takata M, Takeda S, Swenberg JA, Nakamura J
    • Journal Title

      Oncotarget.

      Volume: 7 Pages: 59795-59808

    • DOI

      10.18632/oncotarget.10928

    • NAID

      120005980805

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The role of the Mre11-Rad50-Nbs1 complex in double-strand break repair-facts and myths.2016

    • Author(s)
      Takeda S, Hoa NN, Sasanuma H
    • Journal Title

      J Radiat Res.

      Volume: 57 Suppl 1

    • DOI

      10.1093/jrr/rrw034

    • NAID

      120006027206

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteomics Analysis with a Nano Random Forest Approach Reveals Novel Functional Interactions Regulated by SMC Complexes on Mitotic Chromosomes.2016

    • Author(s)
      Ohta S, Montano-Gutierrez LF, Alves FL, Ogawa H, Toramoto I, Sato N, Morrison CG, Takeda S, Hudson DF, Rappsilber J, Earnshaw WC
    • Journal Title

      Mol Cell Proteomics.

      Volume: 15 Pages: 2802-2818

    • DOI

      10.1074/mcp.m116.057885

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Repriming by PrimPol is critical for DNA replication restart downstream of lesions and chain-terminating nucleosides.2016

    • Author(s)
      Kobayashi K, Guilliam TA, Tsuda M, Yamamoto J, Bailey LJ, Iwai S, Takeda S, Doherty AJ, Hirota K.
    • Journal Title

      Cell Cycle

      Volume: 15(15) Pages: 1997-2008

    • DOI

      10.1080/15384101.2016.1191711

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In vivo evidence for translesion synthesis by the replicative DNA polymerase δ.2016

    • Author(s)
      Hirota K, Tsuda M, Mohiuddin, Tsurimoto T, Cohen IS, Livneh Z, Kobayashi K, Narita T, Nishihara K, Murai J, Iwai S, Guilbaud G, Sale JE, Takeda S.
    • Journal Title

      Nucleic Acids Res.

      Volume: 44(15) Pages: 7242-50

    • DOI

      10.1093/nar/gkw439

    • NAID

      120006338056

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deazaflavin Inhibitors of Tyrosyl-DNA Phosphodiesterase 2 (TDP2) Specific for the Human Enzyme and Active against Cellular TDP22016

    • Author(s)
      Marchand C, Abdelmalak M, Kankanala J, Huang SY, Kiselev E, Fesen K, Kurahashi K, Sasanuma H, Takeda S, Aihara H, Wang Z, Pommier Y
    • Journal Title

      ACS Chemical Biology

      Volume: 11 Pages: 1925-1933

    • DOI

      10.1021/acschembio.5b01047

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Oxidative stress at low levels can induce clustered DNA lesions leading to NHEJ mediated mutations.2016

    • Author(s)
      Sharma V, Collins LB, Chen TH, Herr N, Takeda S, Sun W, Swenberg JA, Nakamura J
    • Journal Title

      Oncotarget

      Volume: 7 Pages: 25377-25390

    • DOI

      10.18632/oncotarget.8298

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The role of HERC2 and RNF8 ubiquitin E3 ligases in the promotion of translesion DNA synthesis in the chicken DT40 cell line.2016

    • Author(s)
      Mohiuddin, Kobayashi S, Keka IS, Guilbaud G, Sale J, Narita T, Abdel-Aziz HI, Wang X, Ogawa S, Sasanuma H, Chiu R, Oestergaard VH, Lisby M, Takeda S.
    • Journal Title

      DNA Repair (Amst)

      Volume: 40 Pages: 64-76

    • DOI

      10.1016/j.dnarep.2016.02.002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Chemical Incorporation of Chain-Terminating Nucleoside Analogs as 3'-Blocking DNA Damage and Their Removal by Human ERCC1-XPF Endonuclease.2016

    • Author(s)
      Yamamoto J, Takahata C, Kuraoka I, Hirota K, Iwai S.
    • Journal Title

      Molecules

      Volume: 21(6)

    • DOI

      10.3390/molecules21060766

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Local potentiation of stress-responsive genes by upstream noncoding transcription2016

    • Author(s)
      Takemata N, Oda A, Yamada T, Galipon J, Miyoshi T, Suzuki Y, Sugano S, Hoffman CS, Hirota K, Ohta K.
    • Journal Title

      Nucleic Acids Res

      Volume: 印刷中 Pages: 5174-5189

    • DOI

      10.1093/nar/gkw142

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Mutator Phenotype and DNA Double-Strand Break Repair in BLM Helicase-Deficient Human Cells2016

    • Author(s)
      Suzuki T, Yasui M, Honma M
    • Journal Title

      Molecular and Cellular Biology

      Volume: 36 Pages: 2877-2889

    • DOI

      10.1128/mcb.00443-16

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Impact of Ribonucleotide Backbone on Translesion Synthesis and Repair of 7,8-Dihydro-8-oxoguanine2016

    • Author(s)
      Sassa A, Caglayan M, Rodriguez Y, Beard WA, Wilson SH, Nohmi T, Honma M, Yasui M
    • Journal Title

      Journal of Biological Chemistry

      Volume: 291 Pages: 24314-24323

    • DOI

      10.1074/jbc.m116.738732

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] ビッグデータとAIの実態および適用範囲を定量的に明確にする能動的学習の紹介2020

    • Author(s)
      J.B. Brown
    • Organizer
      協和キリン株式会社セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 主流となってきた「ビッグデータAI」の必要性を覆す新人工知能基盤の確立2020

    • Author(s)
      J.B. Brown
    • Organizer
      メディカルジャパン2020
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] BRCA1 and BRCA2 protect transcriptional response to estrogens from abortive catalysis by Topoisomerase II2019

    • Author(s)
      Rahman MM, Sasanuma H, Tsuda M, Morimoto S, Yamada S, Nussenzweig A, Tanaka H, Takeda S
    • Organizer
      FASEB Science Research Conference “The Genetic Recombination and Genome Rearrangements Conference”
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] BRCA1 and BRCA2 protect transcriptional response to estrogens from abortive catalysis by Topoisomerase II2019

    • Author(s)
      Takeda S
    • Organizer
      2019 International Conference: Korean Society for Molecular and Cellular Biology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] BRCA1 and BRCA2 protect transcriptional response to estrogens from abortive catalysis by Topoisomerase II2019

    • Author(s)
      Takeda S
    • Organizer
      The 10th International Symposium on DNA Damage Response & Human Disease, isDDRHD-2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Role of proofreading exonuclease activity of replicative polymerase ε in replication fork slowing at DNA damage2019

    • Author(s)
      Tsuda M, Abe T, Tsurimoto T, Shibata T, Takeda S, Hirota K
    • Organizer
      分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 複製ポリメラーゼεの校正活性はカンプトテシンによるDNA損傷における安全なフォーク停止に寄与する2019

    • Author(s)
      Hirota K
    • Organizer
      核酸医薬学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 複製ポリメラーゼεの校正活性はカンプトテシンによるDNA損傷における安全な複製停止に寄与する2019

    • Author(s)
      阿部拓也, 津田雅貴, 釣本俊樹, 柴田武彦, 武田俊一, 廣田耕志
    • Organizer
      染色体ワークショップ
    • Related Report
      2019 Annual Research Report
  • [Presentation] 分裂酵母fbp1遺伝子上流領域における転写因子結合機構の解明2019

    • Author(s)
      幸田和佳奈、千松賢史、廣田耕志
    • Organizer
      酵母遺伝学フォーラム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 分裂酵母fbp1遺伝子上流領域における転写因子結合機構の解明2019

    • Author(s)
      幸田和佳奈、千松賢史、廣田耕志
    • Organizer
      バイオコンファレンス
    • Related Report
      2019 Annual Research Report
  • [Presentation] 分裂酵母fbp1遺伝子上流領域における転写因子結合機構の解明2019

    • Author(s)
      幸田和佳奈、千松賢史、廣田耕志
    • Organizer
      分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 細胞内におけるY Family TLS Polymerasesの機能解明2019

    • Author(s)
      猪又侑里子、阿部拓也、廣田耕志
    • Organizer
      バイオコンファレンス
    • Related Report
      2019 Annual Research Report
  • [Presentation] 細胞内におけるY Family TLS Polymerasesの機能解明2019

    • Author(s)
      猪又侑里子、阿部拓也、廣田耕志
    • Organizer
      分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Deoxyriboseの2’ CH2の相同的組換えでの役割:何故、染色体はDNAなのか2019

    • Author(s)
      柴田武彦、新井直人、美川務、岩崎わかな、廣田耕志
    • Organizer
      第37 回 染色体ワークショップ/第18 回 核ダイナミクス研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 複製ポリメラーゼεの校正活性はDNA損傷における安全なフォーク停止に寄与する2019

    • Author(s)
      津田雅貴、阿部拓也、釣本俊樹、柴田武彦、武田俊一、廣田耕志
    • Organizer
      第37 回 染色体ワークショップ/第18 回 核ダイナミクス研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ネガティブセレクションマーカーを用いた染色体改変技術の構築2019

    • Author(s)
      阿部拓也
    • Organizer
      第8回DNA損傷応答ワークショップ
    • Related Report
      2019 Annual Research Report
  • [Presentation] DNA複製因子TIPINと相同組み換え因子BRCA1の遺伝学的相互作用の解析2019

    • Author(s)
      阿部拓也、吉本侑依、廣田耕志
    • Organizer
      分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] FTO's roles in DNA damage response and underlying mechanism.2019

    • Author(s)
      Weiying LIU, Manabu YASUI, Akira SASSA, Yiyi CAO, Jing XI, Xinyue YOU, Masamitsu HONMA, Yang LUAN
    • Organizer
      The Joint Meeting of The 6th Asian Congress on Environmental Mutagens and The 48th Japanese Environmental Mutagen Society
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Alternate processing pathways of a single ribonucleotide incorporated into DNA and its consequences in human cells.2019

    • Author(s)
      Akira SASSA, Haruto TADA, Ayuna TAKEISHI, Kaho HARADA, Kazuma NAKATANI, Masataka TSUDA, Hiroyuki SASANUMA, Shunichi TAKEDA, Kaoru SUGASAWA, Manabu YASUI, Masamitsu HONMA, Kiyoe URA
    • Organizer
      The Joint Meeting of The 6th Asian Congress on Environmental Mutagens and The 48th Japanese Environmental Mutagen Society
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanistic insight of unique mutations caused by a ribonucleotide embedded into DNA.2019

    • Author(s)
      Ayuna TAKEISHI, Manabu YASUI, Hiroyuki SASANUMA, Shunichi TAKEDA, Kaoru SUGASAWA, Masamitsu HONMA, Kiyoe URA, Akira SASSA
    • Organizer
      The Joint Meeting of The 6th Asian Congress on Environmental Mutagens and The 48th Japanese Environmental Mutagen Society
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 主流となってきた「ビッグデータAI」の必要性を覆す新人工知能基盤の確立2019

    • Author(s)
      J.B. Brown
    • Organizer
      バイオインダストリー協会セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Data volume and tactical decisions for virtual screening-accelerated drug discovery2019

    • Author(s)
      J.B. Brown
    • Organizer
      ETH RETHINK seminar
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 実応用に向けて「能動的計算創薬」の展望2019

    • Author(s)
      J.B. Brown
    • Organizer
      芝蘭会 産学情報交流会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 人工知能(AI)の実態及びAIによる創薬研究活動の加速化の近未来2019

    • Author(s)
      J.B. Brown
    • Organizer
      第一三共株式会社セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Visualizations within chemogenomic active learning reveal how protein descriptors are used and underlying truths about chemogenomic and single target QSAR model utility.2019

    • Author(s)
      J.B. Brown
    • Organizer
      Asian Hub for e-Drug Discovery (AHeDD) 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] BRCA1 ensures genome integrity by eliminating estrogen-induced pathological Topoisomerase II-DNA complexes2019

    • Author(s)
      Takeda S
    • Organizer
      16th Annual Dan L Duncan Comprehensive Cancer Center Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Adaptive Pattern Extraction Underpins Rethinking the Role of Big Data2019

    • Author(s)
      Brown JB
    • Organizer
      ETH Zurich RETHINK Kickoff Symposium
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] K63-ubiquitination signaling promotes end-processing of double-strand breaks for subsequent nonhomologous joining2018

    • Author(s)
      Takeda S, Sasanuma H, Akagawa R
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 2本のDNAの絡みを解消する酵素、トポイソメラーゼ2は、温度変化により触媒反応に失敗する頻度が増えDNA2重鎖切断を作る2018

    • Author(s)
      武田俊一、笹沼博之、Akter S
    • Organizer
      日本ハイパーサーミア学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] DNA repair proteins involved in the repair of pathological Top2 cleavage complex2018

    • Author(s)
      Takeda S
    • Organizer
      Gordon Research Conference, DNA Topoisomerases in Biology and Medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] BRCA1 ensures genome integrity by eliminating estrogen-induced pathological topoisomerase Ⅱ-DNA complexes2018

    • Author(s)
      Takeda S
    • Organizer
      Gordon Research Conference, Genomic Instability
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] XRCC1 inhibits the cytotoxic effect of the stable PARP-DNA complex during base-excision repair2018

    • Author(s)
      Hirota K
    • Organizer
      日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 能動的学習による化合物モデリング、および、導かれた機械学習の真実2018

    • Author(s)
      Brown JB
    • Organizer
      第41回ケモインフォマティクス討論会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Frontiers Unveiled by Active Learning2018

    • Author(s)
      Brown JB, Rakers C, Polash A, Nakano T
    • Organizer
      Asian Hub for e-Drug Discovery 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Active learning of ligand-target interactions to build minimally complex yet maximally predictive interaction models2018

    • Author(s)
      Brown JB
    • Organizer
      International Chemical Biology Society 2018 Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Binary classification metric surfaces2018

    • Author(s)
      Brown JB
    • Organizer
      University of Bonn Workshop on Computational Chemical Biology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Active learning part 1 - concepts and chemogenomic examples2018

    • Author(s)
      Brown JB
    • Organizer
      University of Bonn Workshop on Computational Chemical Biology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Active learning part 2 - assorted topics: de-orphanization, active projections, and hybridization with cross-validation2018

    • Author(s)
      Brown JB
    • Organizer
      University of Bonn Workshop on Computational Chemical Biology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 構造活性相関情報を効率的に選択する能動的学習の医薬品開発応用への最新結果と課題2018

    • Author(s)
      Brown JB
    • Organizer
      構造活性フォーラム2018
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] BRCA1 ensures genome integrity by eliminating estrogen-induced pathological topoisomerase II-DNA complexes2018

    • Author(s)
      Takeda S
    • Organizer
      Life Science Workshop Series 2018, DNA Repair and Radiobiology: Opportunities for Cancer Treatment
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 複製フォーク構成因子とヒストンバリアントH2AX、DNA修復因子の遺伝学的関係性の解析2018

    • Author(s)
      阿部拓也、廣田耕志
    • Organizer
      ヒストンバリアント研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Mre11 Is Essential for the Removal of Lethal Topoisomerase 2 Covalent Cleavage Complexes2017

    • Author(s)
      Takeda S, Sasanuma H
    • Organizer
      ATW2017 Ataxia-Telangiectasia Workshop
    • Place of Presentation
      ミラノ(イタリア)
    • Year and Date
      2017-03-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SUMO化蛋白質を認識するRING型ユビキチンリガーゼRNF4による、スピンドルアセンブリチェックポイント(SAC)活性維持と染色体ロスの防止2017

    • Author(s)
      廣田耕志、高木季代、津田雅貴、村井純子、Keka Islam, 成田岳雄、藤田真梨、笹沼博之、小林純也、武田俊一
    • Organizer
      SUMO研究会
    • Place of Presentation
      関西学院大学(大阪府・大阪市)
    • Year and Date
      2017-01-22
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Mre11 Is Essential for the Removal of Lethal Topoisomerase 2 Covalent Cleavage Complexes2017

    • Author(s)
      Takeda S, Sasanuma H
    • Organizer
      Keystone Symposia, DNA Replication and Recombination
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mre11 is essential for the removal of lethal topoisomerase 2 cleavage2017

    • Author(s)
      Takeda S
    • Organizer
      6th US-Japan DNA Repair Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] DNA複製と転写に必須な酵素、トポイソメラーゼ2は病的な2重鎖DNA切断を高頻度に自然発生する2017

    • Author(s)
      武田俊一
    • Organizer
      第46回放射線による制癌シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] BRCA1 and Mre11 maintain genome integrity by eliminating abortive Topoisomerase complexes2017

    • Author(s)
      Takeda S, Sasanuma H
    • Organizer
      8th international symposium on DNA Damage Response & Human Disease (isDDRHD-2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mre11 is essential for the removal of lethal Topoisomerase2 covalent cleavage complexes2017

    • Author(s)
      Takeda S
    • Organizer
      12th Asia-Pacific Conference on Human Genetics (APCHG2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Why small data and simple models still make sense for therapy discovery.2017

    • Author(s)
      Brown JB
    • Organizer
      Kyoto University-Boehringer Ingelheim joint research meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Smashing phantoms: rectifying views on big data and complex AI in drug discovery and chemical biology.2017

    • Author(s)
      Brown JB
    • Organizer
      3rd Bioinformatics Agora
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Less is more: distilling human interpretable simplicity from models of large qHTS result matrices.2017

    • Author(s)
      Brown JB
    • Organizer
      100th RACI Congress, Asian Hub for e-Drug Discovery Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Transcriptional activation via “catch-and-release” translocation of transcription factor Rst2 between activation sites is mediated by local higher-order genome structure2017

    • Author(s)
      Asada R, Hirota K
    • Organizer
      The 9th International Fission Yeast Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 局所的ゲノム高次構造を介した転写因子の標的配列結合タイミング制御機構の解析2017

    • Author(s)
      浅田隆大、廣田耕志
    • Organizer
      クロマチン動構造ワークショップ
    • Related Report
      2017 Annual Research Report
  • [Presentation] 長鎖 non-coding RNA 転写による クロマチン構造制御メカニズムの解明2017

    • Author(s)
      千松賢史、廣田耕志
    • Organizer
      クロマチン動構造ワークショップ
    • Related Report
      2017 Annual Research Report
  • [Presentation] In vivo evidence for translesion DNA synthesis by replicative DNA polymeraseδ2017

    • Author(s)
      Hirota K
    • Organizer
      US-JP DNA repair work meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 非コードRNAの転写開始によって誘導されるクロマチン再編成の転写や組換えにおける役割2017

    • Author(s)
      廣田耕志
    • Organizer
      遺伝研研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] オーキシンデグロンシステムを用いたトポイソメラーゼ1の細胞内機能の解析2017

    • Author(s)
      梅村小雪、廣田耕志
    • Organizer
      バイオコンフェレンス
    • Related Report
      2017 Annual Research Report
  • [Presentation] metabolic stress-induced lncRNA(mlonRNA)転写はクロマチン再編成を誘導し、転写と減数分裂期組換えを活性化させる2017

    • Author(s)
      千松賢史、廣田耕志
    • Organizer
      バイオコンフェレンス
    • Related Report
      2017 Annual Research Report
  • [Presentation] The establishment of highly sensitive and quantitative analysis assay to detect chromosome loss using HSV-TK2017

    • Author(s)
      鈴木雄也、廣田耕志
    • Organizer
      バイオコンフェレンス
    • Related Report
      2017 Annual Research Report
  • [Presentation] The regulation of Cohesin in higher eukaryotes2017

    • Author(s)
      阿部拓也、廣田耕志
    • Organizer
      Molecular and Cellular biology meeting in TMU
    • Related Report
      2017 Annual Research Report
  • [Presentation] A method to evaluate the frequency of aneuploidy2017

    • Author(s)
      阿部拓也、廣田耕志
    • Organizer
      SMC proteins
    • Related Report
      2017 Annual Research Report
  • [Presentation] metabolic stress-induced lncRNA(mlonRNA)転写によるクロマチン再編成は、転写と減数分裂期組換えを活性化する2017

    • Author(s)
      千松賢史、廣田耕志
    • Organizer
      染色体ワークショップ
    • Related Report
      2017 Annual Research Report
  • [Presentation] DNA トポロジーによるヌクレオソームポジションの規定と転写制御2017

    • Author(s)
      浅田隆大、廣田耕志
    • Organizer
      染色体ワークショップ
    • Related Report
      2017 Annual Research Report
  • [Presentation] 局所的ゲノム高次構造を介した転写因子の標的配列結合タイミング制御機構の解析2017

    • Author(s)
      恒川千明、廣田耕志
    • Organizer
      染色体ワークショップ
    • Related Report
      2017 Annual Research Report
  • [Presentation] metabolic stress-induced lncRNA(mlonRNA)転写はクロマチン再編成を誘導し、転写と減数分裂期組換えを活性化させる2017

    • Author(s)
      千松賢史、廣田耕志
    • Organizer
      分子生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The establishment of highly sensitive and quantitative analysis assay to detect chromosome loss using HSV-TK2017

    • Author(s)
      鈴木雄也、廣田耕志
    • Organizer
      分子生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ALC1クロマチンリモデリング因子のゲノム維持における働き2017

    • Author(s)
      廣田耕志
    • Organizer
      分子生物学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] オーキシンデグロンシステムを用いたトポイソメラーゼ1の細胞内機能の解析2017

    • Author(s)
      梅村小雪、廣田耕志
    • Organizer
      分子生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] TK6及び変異株を用いたヌクレオチド除去修復機構におけるゲノム全体修復と転写共役修復を区別する方法の開発2017

    • Author(s)
      中村真生、鵜飼明子、佐々彰、髙部道仁、福田隆之、髙村岳樹、本間正充、安井学
    • Organizer
      日本環境変異原学会第46回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] TK6及びそのDNA修復遺伝子破壊変異体を用いた高感度遺伝毒性試験法の開発2017

    • Author(s)
      福田隆之、中村真生、佐藤亮佑、藤原聖、佐々彰、鵜飼明子、武田俊一、安井学、本間正充
    • Organizer
      日本環境変異原学会第46回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] SUMO化蛋白質を認識するRING型ユビキチンリガーゼRNF4による染色体恒常性維持機構の解明2017

    • Author(s)
      廣田耕志
    • Organizer
      ヒストンバリアント研究会
    • Place of Presentation
      東北大学(宮城県・仙台市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] DNA中の酸化リボヌクレオチドがDNA複製および修復機構に及ぼす影響2016

    • Author(s)
      佐々彰,Caglayan M, Beard WA, Wilson SH, 能美健彦,本間正充,安井学
    • Organizer
      第45回日本環境変異原学会
    • Place of Presentation
      つくば国際会議場(茨城県・つくば市)
    • Year and Date
      2016-11-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] In vivo evidence for translesion synthesis by the replicative DNA polymeraseδ2016

    • Author(s)
      Hirota K, Tsuda M, Sale J, Takeda S
    • Organizer
      The 10th 3R Symposium
    • Place of Presentation
      ホテル一畑(島根県・松江市)
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ctf18-RFC bound to Polεloads PCNA efficiently2016

    • Author(s)
      Fujisawa R, Ohashi E, Hirota K, Tsurimoto T
    • Organizer
      The 10th 3R Symposium
    • Place of Presentation
      ホテル一畑(島根県・松江市)
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Determination of genotoxic potential by comparison of structurally related azo dyes using DNA repair-deficient DT40 mutant panels2016

    • Author(s)
      Ooka M, Kobayashi K, Abe T, Akiyama K, Hada M, Takeda S, Hirota K
    • Organizer
      The 10th 3R Symposium
    • Place of Presentation
      ホテル一畑(島根県・松江市)
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The proofreading exonuclease activity of replicative polymerase ε contributes to cellular tolerance of cytarabine(Ara-C)2016

    • Author(s)
      Tsuda M, Takeda S, Hirota K
    • Organizer
      The 10th 3R Symposium
    • Place of Presentation
      ホテル一畑(島根県・松江市)
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Elucidation of the chromatin reconstitution mechanism during transcriptional repression of Schizosaccharomyces pombe fdp12016

    • Author(s)
      Umeda M, Hirota K
    • Organizer
      The 10th 3R Symposium
    • Place of Presentation
      ホテル一畑(島根県・松江市)
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chromatin determinants of the inner-centromera rely on replication factors with functions that impart cohesion2016

    • Author(s)
      Abe T, Branzei D, Kawasumi R
    • Organizer
      The 10th 3R Symposium
    • Place of Presentation
      ホテル一畑(島根県・松江市)
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Essential role of the Mre11-Rad50-Nbs1 complex in preventing the endogenous accumulation of lethal Topoisomerase2-DNA-cleavage complex2016

    • Author(s)
      Takeda S
    • Organizer
      The 6th International Conference on Biomedical and Environmental Sciences & Technology, The 7th International Symposium on DNA Damage Response & Human Disease
    • Place of Presentation
      成都(中国)
    • Year and Date
      2016-10-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] In vivo evidence for translation synthesis by the replicative DNA polymerase delta2016

    • Author(s)
      Hirota K, Tsuda M, Sale J, Takeda S
    • Organizer
      DNA Polymerases Meeting
    • Place of Presentation
      ビアリッツ(フランス)
    • Year and Date
      2016-10-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Proofreading Exonuclease Activity of Replicative Polymerasee significantly Contributes to Elimination of Cytarabine (Ara-C)2016

    • Author(s)
      Tsuda M, Takeda S, Hirota K
    • Organizer
      DNA Polymerases Meeting
    • Place of Presentation
      ビアリッツ(フランス)
    • Year and Date
      2016-10-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mre11 Is Essential for the Removal of Lethal Topoisomerase 2 Covalent Cleavage Complexes2016

    • Author(s)
      Takeda S
    • Organizer
      Genomic Instability, Gordon Research Conference
    • Place of Presentation
      香港(中国)
    • Year and Date
      2016-07-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] Practical Chemogenomic Modeling and Molecule Discovery Strategies Unveiled by Active Learning Systems Medicine: Integrative, Qualitative, and Computational Approaches, Reference Module in Biomedical Research (eds. Olaf Wolkenhauer and Ola Engkvist)2019

    • Author(s)
      J.B. Brown
    • Total Pages
      6
    • Publisher
      Elsevier
    • ISBN
      9780128160770
    • Related Report
      2019 Annual Research Report
  • [Book] Selection of informative examples in chemogenomic datasets.2018

    • Author(s)
      Reker D, Brown JB
    • Total Pages
      41
    • Publisher
      Springer Science+Business Media
    • ISBN
      9781493986385
    • Related Report
      2018 Annual Research Report
  • [Remarks] 廣田耕志リサーチマップ

    • URL

      https://researchmap.jp/khirota

    • Related Report
      2019 Annual Research Report
  • [Remarks] 東京都立大学理学研究科化学専攻生物化学研究室ホームページ

    • URL

      http://accafe.jp/biochem_tmu/index.php?FrontPage

    • Related Report
      2019 Annual Research Report
  • [Remarks] 国立医薬品食品衛生研究所 変異遺伝部 TK6細胞ミュータント コンソーシアム

    • URL

      http://www.nihs.go.jp/dgm/tk6.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 世界中の研究者に遺伝子破壊細胞を分与しているTK6 Mutants Consortium

    • URL

      http://www.nihs.go.jp/dgm/tk6.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 武田薬品と国立がんセンターが共同運営する化合物スクリーニングセンター(i-Park)

    • URL

      https://www.takeda.com/ja-jp/who-we-are/company/shonan/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 「京大、人口知能の性能を正確に評価する方法を開発」 日本経済新聞電子版

    • URL

      https://www.nikkei.com/article/DGXLRSP473371_V00C18A3000000/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 研究成果であった能動的学習が ChemMedChem誌表紙選抜

    • URL

      https://onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.201800124?af=R

    • Related Report
      2017 Annual Research Report
  • [Remarks] 京都大学 プレスリリース(日本語)

    • URL

      http://www.kyoto-u.ac.jp/ja/research/research_results/2016/170306_1.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 京都大学 プレスリリース(英語)

    • URL

      http://www.kyoto-u.ac.jp/en/research/research_results/2016/170306_1.htm

    • Related Report
      2016 Annual Research Report
  • [Remarks] 日本経済新聞 プレスリリース

    • URL

      http://www.nikkei.com/article/DGXLRSP438913_Y7A300C1000000/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 京都新聞 掲載記事

    • URL

      http://www.kyoto-np.co.jp/education/article/20170306000124

    • Related Report
      2016 Annual Research Report
  • [Remarks] マイナビニュース 掲載記事

    • URL

      http://news.mynavi.jp/news/2017/03/09/238/

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2016-06-01   Modified: 2021-01-27  

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