Increasing DSB ends mobility with 53BP1 improve Non homologous end joining

2014 Fiscal Year Final Research Report

• Project/Area Number: 23510067
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kanazawa Medical University
• Principal Investigator: HASHIMOTO Mitsumasa 金沢医科大学, 一般教育機構, 准教授 (70293975)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: 53BP1 / Rad18 / TRF2 / DNA二重鎖切断 / テロメア / T-SCE

Outline of Final Research Achievements

53BP1 plays a key role in repair for DNA double strand breaks. 53BP1 binds ends of DSBs and facilitates rejoining of both ends. I and co-authors reported that (1) 53BP1 plays a role in a novel pathway distinct from the Ku-dependent and Artemis-dependent NHEJ (Non homologus end joining) pathways (Genes Cells, 11: 935, 2006). (2) RAD18 interacts with 53BP1 and is recruited to DSB sites in a 53BP1-dependent manner specifically during G1-phase. RAD18 monoubiquitinates 53BP1, consequently, enhances retention of 53BP1 at DSBs site (Nucleic Acids Res., 37: 2176, 2009). Depletion of TRF2 (one of shelterin components) arises dysfunctional and unprotected telomeres. Telomere deprotection activate ATM dependent DNA repair pathway and promote NHEJ. DNA repair proteins including 53BP1 recognize unprotected telomeres as DSBs. I investigated that the interaction between 53BP1 and Rad18 works in the rejoing of telomere ends.

Free Research Field

放射線生物学