Analysis of the early steps of DNA damage response through 9-1-1/TopBP1 interaction

2011 Fiscal Year Final Research Report

• Project/Area Number: 22770172
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Molecular biology
• Research Institution: Kyushu University
• Principal Investigator: OHASHI Eiji 九州大学, 理学研究院, 助教 (90378951)
• Research Collaborator: TSURIMOTO Toshiki 九州大学, 理学研究院, 教授 (30163885)
• Project Period (FY): 2010 – 2011
• Keywords: DNA損傷応答 / チェックポイント / 蛋白質問相互作用 / 細胞内局在 / 試験管内再構築

Research Abstract

The Rad9Husl-Radl(9-1-1) complex, a DNA damage sensor interacts with TopBP1 to activate a signaling pathway. In this study, we found that 911/TopBP1 interaction plays an important role in the signal transduction after their localization to the sites of DNA damage without affecting their localization upon DNA damage. The binding ability of Rad9 to TopBP1 was strongly correlated with the activity of DNA damage response in human cells. Finally, our in vitro results suggest that 9-1-1 has a potential to interact with DNA and the binding ability may be regulated by the interaction with other factors.

Research Products

• [Journal Article] The vital role of polymerase C and REV1 in mutagenic, but not correct, DNA synthesis across benzo[ a] pyrene-dG and recruitment of polymerase C by REV1 to replicationstalled site (2012)
  • Author(s): Hashimoto K, Cho Y, Yang IY, Akagi J, Ohashi E, Tateishi S, de Wind N, Hanaoka F, Ohmori H, and Moriya M.
  • Journal Title: J. Biol. Chem Volume: 287 Pages: 9613-9622
  • Peer Reviewed
• [Journal Article] Human replicative DNA polymerase d can bypass T-T(6-4) ultraviolet photoproducts on template strands (2010)
  • Author(s): Narita T, Tsurimoto T, Yamamoto J, Nishihara K, Ogawa K, Ohashi E, Evans T, Iwai S, Takeda S, and Hirota K.
  • Journal Title: Genes Cells Volume: 15 Pages: 1228-1239
  • Peer Reviewed
• [Journal Article] Stable interaction between the human PCNA loader complex Ctf18-RFC and DNA polymerase e is mediated by the cohesion specific subunits, Ctf18, Dcc1 and Ctf8 (2010)
  • Author(s): Murakami T, Takano R, Takeo S, Taniguchi R, Ogawa K, Ohashi E, and Tsurimoto T.
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 34608-34615
  • Peer Reviewed
• [Journal Article] Casein kinase 2dependent phosphorylation of human Rad9 mediates the interaction between human Rad9-Husl-Rad1 complex and TopBP1 (2010)
  • Author(s): Takeishi Y, Ohashi E, Ogawa K, Masai H, Obuse C, and Tsurimoto T.
  • Journal Title: Genes Cells Volume: 15 Pages: 761-771
  • Peer Reviewed
• [Presentation] Roles of the 9-1-1/TopBP1 interaction for DNA damage responses in human cells (2011)
  • Author(s): Ohashi E, Takeishi Y, Ueda S, and Tsurimoto T.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] ヒト細胞内でのDNA損傷応答における9-1-1/TopBP1相互作用の役割 (2011)
  • Author(s): 大橋英治、武石幸容、上田聡、釣本敏樹
  • Organizer: 第21回DNA複製・組換え・ゲノム安定性制御ワークショップ
  • Place of Presentation: 福津
  • Year and Date: 2011-10-25
• [Presentation] Roles of the human 9-1-1/TopBP1 interaction for DNA damage responses (2011)
  • Author(s): Ohashi E, Takeishi Y, Ueda S, and Tsurimoto T.
  • Organizer: Cold Spring Larbor Laboratory Meeting on" Eukaryotic DNA replication and genome maintenance
  • Place of Presentation: CSH, NY, USA
  • Year and Date: 2011-09-08
• [Presentation] Chromatin association of human Rad9Husl-Radl complex is dependent on TopBP1 but not on the interaction with TopBP1 (2010)
  • Author(s): Ohashi E, Takeishi Y, Ueda S, and Tsurimoto T.
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07