2013 Fiscal Year Final Research Report

Analysis of a novel regulatory mechanism for DNA double-strand break repair by non-homologous end-joining

Research Project

Project/Area Number	23510066
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	Kumamoto University
Principal Investigator	YANO Ken-ichi 熊本大学, パルスパワー科学研究所, 教授 (70311230)
Project Period (FY)	2011 – 2013
Keywords	修復 / DNA損傷 / 非相同末端連結 / DNA二重鎖切断
Research Abstract	Ku and XLF are essential factors for non-homologous end-joining (NHEJ) that is a major mechanism for DNA double-strand break repair. An R57G substitution in XLF protein has been identified in patients with hereditary hypersensitivity to ionizing radiation. In this study, we performed detailed analysis of the interaction between Ku and XLF and evaluated the effects of inositol-6-phosphate, which is known to augment NHEJ in cell-free systems, on the Ku-XLF interaction. Live cell imaging demonstrated that XLF protein with the R57G substitution (XLF R57G) localizes in nucleus and accumulates at sites of DNA damage, similar to wild-type XLF. Ubiquitination was detected in XLF R57G, but not in wild-type XLF, suggesting the causal relationship with hyper-radiosensitivity in patients harboring this mutation.