首页|Di-and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair
Di-and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
NETL
NSTL
万方数据
Histone H3 Lys36(H3K36)methylation and its associated modifiers are crucial for DNA double-strand break(DSB)repair,but the me-chanism governing whether and how different H3K36 methylation forms impact repair pathways is unclear.Here,we unveil the distinct roles of H3K36 dimethylation(H3K36me2)and H3K36 trimethylation(H3K36me3)in DSB repair via non-homologous end joining(NHEJ)or homologous recombination(HR).Yeast cells lacking H3K36me2 or H3K36me3 exhibit reduced NHEJ or HR efficiency.yKu70 and Rfa1 bind H3K36me2-or H3K36me3-modified peptides and chromatin,respectively.Disrupting these interactions impairs yKu70 and Rfa1 recruit-ment to damaged H3K36me2-or H3K36me3-rich loci,increasing DNA damage sensitivity and decreasing repair efficiency.Conversely,H3K36me2-enriched intergenic regions and H3K36me3-enriched gene bodies independently recruit yKu70 or Rfa1 under DSB stress.Importantly,human KU70 and RPA1,the homologs of yKu70 and Rfa1,exclusively associate with H3K36me2 and H3K36me3 in a con-served manner.These findings provide valuable insights into how H3K36me2 and H3K36me3 regulate distinct DSB repair pathways,highlighting H3K36 methylation as a critical element in the choice of DSB repair pathway.
histone H3K36 methylationKu70RPAnon-homologous end joininghomologous recombination
Runfa Chen、Meng-Jie Zhao、Yu-Min Li、Ao-Hui Liu、Ru-Xin Wang、Yu-Chao Mei、Xuefeng Chen、Hai-Ning Du
展开 >
Hubei Key Laboratory of Cell Homeostasis,College of Life Sciences,TaiKang Center for Life and Medical Sciences,Frontier Science Center for Immunology and Metabolism,Hubei Clinical Research Center of Emergency and Resuscitation,Emergency Center of Zhongnan Hospital,Wuhan University,Wuhan 430072,China
Hubei Key Laboratory of Cell Homeostasis,College of Life Sciences,TaiKang Center for Life and Medical Sciences,Frontier Science Center for Immunology and Metabolism,Wuhan University,Wuhan 430072,China
National Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaFundamental Research Funds for the Central UniversitiesApplication Fundamental Frontier Foundation of Wuhan
NETL
NSTL
万方数据
