Biochemical analysis of post-replication repair pathway involved in induced mutagenesis

2011 Fiscal Year Final Research Report

• Project/Area Number: 20310030
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Nagoya University (2011); Hiroshima University (2008-2010)
• Principal Investigator: MASUDA Yuji 名古屋大学, 環境医学研究所, 准教授 (30273866)
• Co-Investigator(Kenkyū-buntansha): KAMIYA Kenji 広島大学, 原爆放射線医科学研究所, 教授 (60116564)
• Project Period (FY): 2008 – 2011
• Keywords: 複製後修復 / 損傷乗り越え DNA 合成 / 突然変異誘発 / PCNA / RAD6-RAD18 / HLTF

Research Abstract

DNA lesions produced by ionizing radiation and environmental mutagen inhibit DNA replication. Stalling replication would lead to cell death if it persisted. Cells have mechanisms (post-replication repair, PRR) to restore DNA replication to survive against DNA-damaging agents. PRR is involved in induced mutagenesis. In this study, we purifiedenzymes required for PRR, reconstituted biochemical reactions with the enzymes and analyzed molecular mechanisms of the PRR.

Research Products

• [Journal Article] In vitro studies of exchanges between replicative and translesion DNA polymerases in eukaryotic post-replication repair pathway (2012)
  • Author(s): Masuda Y
  • Journal Title: Genes Environ Volume: (in press)
  • Peer Reviewed
• [Journal Article] Molecular nature of radiation injury and DNA repair disorders associated with radiosensitivity. (2012)
  • Author(s): Masuda Y, Kamiya K
  • Journal Title: Int. J. Hematol. Volume: 95 Pages: 239-245
  • Peer Reviewed
• [Journal Article] Asymmetric nature of two subunits of RAD18, a RING-type ubiquitin ligase E3, in the human RAD6A-RAD18 ternary complex. (2012)
  • Author(s): Masuda Y, Suzuki M, Kawai H, Suzuki F, Kamiya K.
  • Journal Title: Nucleic Acids Res Volume: 40 Pages: 1065-1076
  • Peer Reviewed
• [Journal Article] Proceedings of the Ninth International Conference on Tritium Science and Technology: Development of a Sensitive Assay System for Tritium Risk Assessment Using Rev1 Transgenic Mouse. (2011)
  • Author(s): Toyoshima M, Honda H, Watanabe H, Masuda Y, Kamiya K.
  • Journal Title: Fusion Science and Technology. Volume: 60 Pages: 1204-1207
  • Peer Reviewed
• [Journal Article] The Rev1 translesion synthesis polymerase has multiple distinct DNA binding modes. (2011)
  • Author(s): de Groote FH, Jansen JG, Masuda Y, Shah DM, Kamiya K, de Wind N, Siegal G.
  • Journal Title: DNA Repair(Amst) Volume: 10 Pages: 915-25
  • Peer Reviewed
• [Journal Article] Generation and evaluation of an anti-REV1 monoclonal antibody. (2010)
  • Author(s): Tachibana N, Iwamoto T, Kawamura T, Masuda Y, Mori T, Kamiya K.
  • Journal Title: Hiroshima J. Med. Sci. Volume: 59 Pages: 51-56
  • Peer Reviewed
• [Journal Article] Regulation of DNA polymerase POLD4 influences genomic instability in lung cancer. (2010)
  • Author(s): Huang QM, Tomida S, Masuda Y, Arima C, Cao K, Kasahara TA, Osada H, Yatabe Y, Akashi T, Kamiya K, Takahashi T, Suzuki M.
  • Journal Title: Cancer Res. Volume: 70 Pages: 8407-8416
  • Peer Reviewed
• [Journal Article] DNA replication-coupled PCNA mono-ubiquitination and polymerase switching in a human in vitrosystem. (2010)
  • Author(s): Masuda Y, Piao J, Kamiya K
  • Journal Title: J. Mol. Biol Volume: 396 Pages: 487-500
  • Peer Reviewed
• [Journal Article] Specific amino acid residues are involved in substrate discrimination and template binding of human REV1 protein. (2010)
  • Author(s): Piao J, Masuda Y, Kamiya K
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 392 Pages: 140-144
  • Peer Reviewed
• [Journal Article] Roles of POLD4, smallest subunit of DNA polymerase delta, in nuclear structures and genomic stability of human cells. (2010)
  • Author(s): Huang QM, Akashi T, Masuda Y, Kamiya K, Takahashi T, Suzuki M.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 391 Pages: 542-546
  • Peer Reviewed
• [Journal Article] Translesional DNA synthesis through a C8-guanyl adduct of 2-amino-1-methyl-6- phenylimidazo[4,5-b]pyridine (PhIP) in vitro: REV1 inserts dC opposite the lesion, and DNA polymerase kappa potentially catalyzes extension resaction from the 3'-dC terminus (2009)
  • Author(s): Fukuda H, Takamura-Enya T, Masuda Y, Nohmi T, Seki C, Kamiya K, Sugimura T, Masutani C, Hanaoka F, Nakagama H.
  • Journal Title: J. Biol. Chem Volume: 284 Pages: 255 5-25592
  • Peer Reviewed
• [Journal Article] Induced mutagenesis and translesion DNA synthesis-structure and function of REV1 (2008)
  • Author(s): Masu Y, amiya K K
  • Journal Title: Seik u Volume: 80 Pages: 843-846
• [Journal Article] Biochemical analysis of human PIF1 helicase ctions o ts N-te inal domain. (2008)
  • Author(s): Gu , agak Y Masuda Y, Kamiya K
  • Journal Title: Nucleic Acids Res Volume: 36 Pages: 6295-6308
  • Peer Reviewed
• [Journal Article] DNA damage induc d ubiquity ti of C2 sub it of RFC complex. (2008)
  • Author(s): Tomida J, Masuda Y, Hiroaki H, Ishikawa T, Song I, Tsurimoto T, Tateishi S, Shiomi T, Kamei Y, Kim J, Kamiya K, Vaziri C, Ohmori H, Todo T.
  • Journal Title: J. Biol. Chem Volume: 283 Pages: 9071-9079
  • Peer Reviewed
• [Presentation] PCNAのユビキチン化に関わるユビキチンリガーゼ(E3)の解 (2012)
  • Author(s): 増田雄司
  • Organizer: 遺伝学研究所研究集会「ユビキチン・SUMOによる DNA 複製及び DNA 修復系の制御」
  • Place of Presentation: 立遺伝学研究所:三島(招待講演)
  • Year and Date: 2012-02-09
• [Presentation] D N A損傷トレランスと複製後修復経路の機能 (2011)
  • Author(s): 増田雄司、鈴木美紀、神谷研二
  • Organizer: 日本分子生物学会第34回年会
  • Place of Presentation: パシフィコ横浜:横浜(招待講演)
  • Year and Date: 2011-12-14
• [Presentation] 誘発突然変異とその制御機構-PCNAのユビキチン修飾の分子機構の解析から- (2011)
  • Author(s): 増田雄司
  • Organizer: 名古屋大学環境医学研究所
  • Place of Presentation: 群馬大学 昭和キパス ャン :前橋(招待講演)
  • Year and Date: 2011-12-09
• [Presentation] 放射線によるDNA損傷と複製後修復経路の機能 (2011)
  • Author(s): 増田雄司、鈴木美紀、神谷研二
  • Organizer: 日本放射線影響学会第54回大会
  • Place of Presentation: 神戸商工会議所会館:神戸(招待講演)
  • Year and Date: 2011-11-19
• [Presentation] DNA damage tolerance and molecular mechanism of PCNA ubiquitination (2011)
  • Author(s): Masuda Y, Suzuki M, Kamiya K
  • Organizer: 14th International Congress of Radiation Research
  • Place of Presentation: Warsaw, Poland
  • Year and Date: 2011-08-30
• [Presentation] 突然変異誘発経路の制御機構～PCNAのユビキチン修飾の生化学的解析から (2011)
  • Author(s): 増田雄
  • Organizer: 平成 23 年度 日本環境変異原学会公開シンポジウム
  • Place of Presentation: 慶應義塾大 共立キャンパス:東京(招待講演)
  • Year and Date: 2011-05-28
• [Presentation] Biochemical analysis of PCNA-ubiquitination in humans (2010)
  • Author(s): Masuda Y, Suzuki M, Kawai H, Hishiki A, Hashimoto H, uzuki F, S ami K ya K
  • Organizer: The 7th 3R (Replication, Recombination and Repair) Symposium
  • Place of Presentation: 富山
  • Year and Date: 2010-10-26
• [Presentation] P C N Aのユビキチン化反応の生化学的解析 (2010)
  • Author(s): 増田雄司、鈴木美紀、可合秀彦、菱木麻美、橋本 博、鈴木文男、神谷研二
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-20
• [Presentation] Dynamics of human replicatio f ctors and DNA olym rase switching (2009)
  • Author(s): Masuda Y
  • Organizer: Mini-Workshop on "DNA Polymerase"
  • Place of Presentation: 奈良先端科学技 大学院・大学:生駒(招待講演)
  • Year and Date: 2009-11-27
• [Presentation] 複製後修復経路におけるDNAポリメラーゼ交換反応の生化学的解析 (2009)
  • Author(s): 増田雄司、神谷研二
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
  • Year and Date: 2009-11-12
• [Presentation] Reconstitution of DNA replication reactions with purified recombinant human proteins in vitro (2009)
  • Author(s): Masuda Y, Suzuki M, Piao, J, Gu Y, Tsurumoto T, Kamiya K
  • Organizer: 2nd Asian Congress of Radiation Research
  • Place of Presentation: Korea
  • Year and Date: 2009-05-17
• [Presentation] ヒトRAD6-RAD18 によるPCNAのユビキチン化反応の分子機構 (2008)
  • Author(s): 増田雄司、神谷研二
  • Organizer: 日本放射線影響学会第51回大会
  • Place of Presentation: 北九州
  • Year and Date: 2008-11-19
• [Remarks]
  • URL: http://www.riem.nagoya-u.ac.jp/genome.html
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/exponc/inhtml