Analysis for regulation of RNR activity during DNA damage repair

• Project/Area Number: 21590315
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Hamamatsu University School of Medicine (2010-2011); Nagoya City University (2009)
• Principal Investigator: NIIDA Hiroyuki 浜松医科大学, 医学部, 准教授 (20336671)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2011: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 細胞医化学 / DNA修復

Research Abstract

A balanced deoxyribonucleotide(dNTP) supply is essential for DNA repair. Here, we found that ribonucleotide reductase(RNR) subunits RRM1 and RRM2 accumulated very rapidly at damage sites. RRM1 bound physically to Tip60. Chromatin immunoprecipitation analyses of cells with an I-SceI cassette revealed that RRM1 bound to a damage site in a Tip60-dependent manner. Active RRM1 mutants lacking Tip60 binding failed to rescue an impaired DNA repair in RRM1-depleted G1-phase cells. Inhibition of RNR recruitment by an RRM1 C-terminal fragment sensitized cells to DNA damage. We propose that Tip60-dependent recruitment of RNR plays an essential role in dNTP supply for DNA repair.

Research Products

• [Journal Article] Mechanisms of dNTP supply that play an essential role in maintaining genome integrity in eukaryotic cells (2010)
  • Author(s): Niida H, Shimada M, Murakami H, Nakanishi M
  • Journal Title: Cancer Sci Volume: 101 Pages: 2505-2509
  • NAID: 10027834110
• [Journal Article] Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase (2010)
  • Author(s): Niida H, Katsuno Y, Sengoku M, Shimada M, Yukawa M, Ikura M, Ikura T, Kohno K, Shima H, Suzuki H, Tashiro S, Nakanishi M
  • Journal Title: Genes Dev Volume: 24 Pages: 333-338
  • NAID: 130007000033
• [Presentation] Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase (2011)
  • Author(s): 丹伊田浩行
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2011-09-23
• [Presentation] Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase (2011)
  • Author(s): 丹伊田浩行
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都国際会議場
• [Presentation] Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase (2010)
  • Author(s): 丹伊田浩行
  • Organizer: 日本放射線影響学会
  • Place of Presentation: 京都テルサ
  • Year and Date: 2010-10-20
• [Presentation] Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase (2010)
  • Author(s): 丹伊田浩行
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: 京都テルサ
• [Presentation] Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites is required for DNA repair during G1 phase (2009)
  • Author(s): 丹伊田浩行
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-11
• [Presentation] Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase (2009)
  • Author(s): 丹伊田浩行
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜