Di-and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair  

作　　者：Runfa Chen Meng-Jie Zhao Yu-Min Li Ao-Hui Liu Ru-Xin Wang Yu-Chao Mei Xuefeng Chen Hai-Ning Du 

机构地区：[1]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 [2]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

出　　处：《Science China(Life Sciences)》2024年第6期1089-1105,共17页中国科学（生命科学英文版）

基　　金：supported by the National Key Research and Development Program of China(2019YFA0802501);the National Natural Science Foundation of China(32270617,31971231);the Fundamental Research Funds for the Central Universities(2042022dx0003);the Application Fundamental Frontier Foundation of Wuhan(2020020601012225)。

摘　　要：Histone H3 Lys36(H3K36)methylation and its associated modifiers are crucial for DNA double-strand break(DSB)repair,but the mechanism 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.y Ku70 and Rfa1 bind H3K36me2-or H3K36me3-modified peptides and chromatin,respectively.Disrupting these interactions impairs y Ku70 and Rfa1 recruitment 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 y Ku70 or Rfa1 under DSB stress.Importantly,human KU70 and RPA1,the homologs of y Ku70 and Rfa1,exclusively associate with H3K36me2 and H3K36me3 in a conserved 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.

关 键 词：histone H3K36 methylation KU70 RPA non-homologous end joining homologous recombination 

分 类 号：Q75[生物学—分子生物学]