Mechanism of reactivation of replication forks stalled by DNA damage

• Project/Area Number: 24710059
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Hiroshima University
• Principal Investigator: MIYAMOTO Mayumi 広島大学, 理学(系)研究科(研究院), 特任助教 (10457278)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: DNA複製 / 相同組換え

Research Abstract

DNA replication forks are stalled when they encounter genome damage. However, it has not been fully elucidated how stalled replication forks are reactivated and complete DNA synthesis in higher eukaryotes. In the present study we analyzed the sensitivity of DNA repair mutants to various DNA-protein cross-link (DPC) agents and accumulation of DNA double-strand breaks (DSB). Cells deficient in homologous recombination (HR) were hypersensitive to DPC-inducing agents. The HR-deficient but not wild type cells accumulated DSBs upon treatment with DPC-inducing agents. These results suggest that replication forks that are stalled by DPCs undergo breakage and that the resulting DSB ends are processed by HR to resume DNA replication.

Research Products

• [Journal Article] Translocation and stability of replicative DNA helicases upon encountering DNA-protein cross-links (2013)
  • Author(s): Toshiaki Nakano
  • Journal Title: Journal of Biological Chemistry Volume: 288 Issue: 7 Pages: 4649-4658
  • DOI: 10.1074/jbc.m112.419358
  • Peer Reviewed
• [Presentation] 抗がん剤が誘発する致死ゲノム損傷の解析 (2013)
  • Author(s): 大場俊也,謝明章,Mahmoud Shoulkamy,Amir Salem,宮本(松原)真由美,中野敏彰,井出博
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸市
• [Presentation] 放射線照射腫瘍におけるDNA二本鎖切断とDNA-タンパク質クロスリンク損傷の解析 (2013)
  • Author(s): 中野敏彰,光定雄介,宮本(松原)真由美,平山亮一,鵜澤玲子,古澤佳也,井出博
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森市
• [Presentation] 放射線照射腫瘍におけるDNA二本鎖切断とDNA-タンパク質クロスリンク損傷の解析 (2013)
  • Author(s): 中野敏彰
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: 青森
• [Presentation] 抗がん剤が誘発する致死ゲノム損傷の解析 (2013)
  • Author(s): 大場俊也
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] DNA-タンパク質クロスリンク損傷が誘発する非標的転写エラー (2012)
  • Author(s): 中野敏彰,大内綾,宮本(松原)真由美,井出博
  • Organizer: 日本環境変異原学会第41回大会
  • Place of Presentation: 静岡市
• [Presentation] アルデヒド化合物が誘発するDNA-タンパク質クロスリンク損傷の解析 (2012)
  • Author(s): Mahmoud Shoulkamy,大場俊也,宮本(松原)真由美,中野敏彰,井出博
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 仙台市