Cellular response to DNA single-strand break and its repair

• Project/Area Number: 24310037
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Tohoku University
• Principal Investigator: YASUI Akira 東北大学, 加齢医学研究所, 教授 (60191110)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2012: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: single-strand break / DNA repair / PARP1 / Poly(ADP-ribosyl)ation / MMS / Homologous recombination / 単鎖切断 / ポリADPリボシレーション / DNA単鎖切断 / DNA修復 / APエンドヌクレアーゼ / ポリADPリボースポリメラーゼ / 相同組換え / ポリADPリボシル化 / エンド/エキソヌクレアーゼ / 癌治療

Outline of Final Research Achievements

DNA single-strand break is thought to be the most frequent type of DNA damage, but its significance in biological function and its repair within human cell remain to be determined. Here we identified genes involved in the regulation of SSB repair in human cell. ONe gene encodes a protein, which interacts directly with PARP1 within human cell. When its expression was suppressed with siRNA, poly(ADP-ribiosyl)ation was decreased after treatment of cells with MMS and cellular resistance to MMS decreased. Its recombinant protein has an endonuclease against AP site as well as exonuclease to both 5' and 3' directions. These data suggest that while PARP1 is able to bind SSB, for its effective activation PARP1 requires gap produced by this protein. Further analysis is required to elucidate the importance of this protein in cellular survival and oncogenesis.

Research Products

• [Journal Article] Novel method for site-specific induction of oxidative DNA damage reveals differences in recruitment of repair proteins to heterochromatin and euchromatin (2014)
  • Author(s): Lan L, Nakajima S, Wei L, Sun L, Hsieh CL, Sobol RW, Bruchez M, Van Houten B, Yasui A, Levine AS.
  • Journal Title: Nucleic Acids Res. Volume: 42 Pages: 2330-45
  • DOI: 10.1093/nar/gkt1233
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The BRCA1/BARD1-interacting protein OLA1 functions in centrosome regulation. (2014)
  • Author(s): Matsuzawa A, Kanno S, Nakayama M, Mochiduki H, Wei L, Shimaoka T, Furukawa Y, Kato K, Shibata S, Yasui A, Ishioka C, Chiba N.
  • Journal Title: Molecular Cell Volume: 53 Pages: 101-114
  • DOI: 10.1016/j.molcel.2013.10.028
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel Methods for sire-specific induction of oxidative DNA damage reveals differences in recruitment of repair proteins to heterochromatin and euchromatin (2014)
  • Author(s): Lan L, Nakajima S, Wei L, Sun L, Hsieh CL, Sobol RW, Bruchez M, van Houten B, Yasui A, and Levine AS
  • Journal Title: Nucleic Acids Res Volume: 196 Pages: 443-453
  • DOI: 10.1534/genetics.113.159541
  • Peer Reviewed
• [Journal Article] Damage response of XRCC1 at sites of DNA single strand breaks is regulated by phosphorylation and ubiquitination after degradation of poly (ADP) ribose. (2013)
  • Author(s): Leizhen Wei,Satoshi Nakajima, Ching-Lung Hsieh, Shinichiro Kanno, Mitsuko Masutani, Arthur S. Levine1, Akira Yasui, Li Lan
  • Journal Title: J Cell Sci Volume: 126(Pt 19) Pages: 4414-23
  • DOI: 10.1242/jcs.128272
  • Peer Reviewed
• [Journal Article] Curcumin suppresses multiple DNA damage response pathways and has potency as a sensitizer to PARP inhibitor. (2013)
  • Author(s): Ogiwara H, Ui A, Shiotani B, Zou L, Yasui A, Kohno T
  • Journal Title: Carciogenesis Volume: 34 Pages: 2486-2497
  • DOI: 10.1093/carcin/bgt240
  • Peer Reviewed
• [Journal Article] Alternative excision repair pathways. (2013)
  • Author(s): Yasui A
  • Journal Title: Cold Spring Harb Perspect Biol. Volume: 8
  • DOI: 10.1371/journal.pone.0060208
  • Peer Reviewed
• [Journal Article] Polycomb group protein PHF1 regulates p53-dependent cell growth arrest and apoptosis. (2013)
  • Author(s): Yang Y, Wang C, Zhang P, Gao K, Wang D, Yu H, Zhang T, Jiang S, Hexige S, Hong Z, Yasui A, Liu JO, Huang H, Yu L
  • Journal Title: J Biol Chem Volume: 288 Pages: 529-539
  • DOI: 10.1074/jbc.m111.338996
  • Peer Reviewed
• [Journal Article] The role of hnRPULI involved in DNA damage response is related to PARPL. (2013)
  • Author(s): Hong Z, et al.
  • Journal Title: Plos One Volume: (In press)
  • Peer Reviewed
• [Journal Article] Alternative excision repair pathways (2013)
  • Author(s): Yasui A.
  • Journal Title: Cold Spring Harb. Perspect. Biol. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Molecular basis for H3K36me3 recognition by the tudor domains of PHFL (2012)
  • Author(s): Musselman CA, et al.
  • Journal Title: Nat. Struct. Mol. Biol. Volume: 19 Pages: 1266-1272
  • Peer Reviewed
• [Presentation] Single-strand breaks and PARP activation (2012)
  • Author(s): 安井 明
  • Organizer: 第4回日米DNA修復会議
  • Place of Presentation: ワシントンDC, 米国(招待講演)