组蛋白H2B单泛素化参与DNA损伤修复的调控机制  

Regulation of DNA Repair by Mono-Ubiquitination of H2B

作　　者：曾鸣[1] 郭莲娣[1] 王鑫[1] 杨娟[1] 王思[1] 汪小波[1] 翁育丁 刘聪[1] 

机构地区：[1]四川大学华西第二医院,成都610041

出　　处：《中国科学：生命科学》2014年第7期702-710,共9页Scientia Sinica(Vitae)

基　　金：国家自然科学基金(批准号:31171319)资助项目

摘　　要：作为一种重要的组蛋白修饰形式,H2B的单泛素化(uH2B)广泛地参与DNA复制、基因的表达与转录、DNA损伤修复及异染色质维持等生物学事件.在裂殖酵母中,H2B的单泛素化发生在其羧基端的119位赖氨酸(K119),并依赖于Rhp6/Bre1泛素连接酶复合体.研究表明,uH2B通过破坏H2A/H2B二聚体的结构促进mRNA在转录过程中的延伸,同时促进H3K4的三甲基化激活基因的表达及参与DNA损伤修复.本研究发现,Rhp6能够对核糖核苷酸还原酶抑制基因(Spd1)位点进行活跃的染色质修饰,促进H2B的单泛素化并抑制基因表达,从而促进dNTP的合成并调控DNA复制及损伤修复.重要的是,本研究发现,该过程不依赖于H3K4而决定于H3K9的三甲基化.同时uH2B直接在DNA双链断裂位点富集,通过改变染色质的结构参与DNA损伤修复,该过程中可能存在其他更为复杂的分子机制.As an important histone modification, mono-ubiquitination of H2B （uH2B） widely regulates a series of events, including DNA replication, gene expression and transcription, DNA repair and heterochromatin maintenance. In Schizosaccharomyces pombe, uH2B occurs at its C-terminal lysine 119 dependent on Rhp6/Brel complex. Research shows that uH2B activates gene expression and regulates DNA repair via stimulating methylation of H3K4 and promoting mRNA elongation through destroying H2A/H2B dimer. We demonstrate that localization of Rhp6 silences spdl by stimulating mono-ubiquitination of H2B at spd1 region and promoting dNTP synthesis to regulate DNA replication and DNA repair. Importantly, it depends on trimethylation of H3K9 instead of H3H4. Besides, enrichment of uH2B at double strand break site plays an important role in DNA repair through regulating chromatin structure, but the mechanism remains unclear.

关 键 词：DNA修复 DNA双链断裂 H2B单泛素化 Spd1 RNR 

分 类 号：R346[医药卫生—基础医学]