RAGl-mediated ubiquitylation of histone H3 is required for chromosomal V（D）J recombination  

作　　者：Zimu Deng Haifeng Liu Xiaolong Liu 

机构地区：[1]State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

出　　处：《Cell Research》2015年第2期181-192,共12页细胞研究（英文版）

基　　金：Acknowledgments We thank Drs David G Schatz, David Roth, Stephen Desiderio and Martin Gellert for providing recombination plasmids. We are grateful to our colleagues H Chen for animal husbandry and W Bian for cell sorting. This work was supported by grants from National Basic Research Program of China （2013CB835300 and 2012CB518700）, National Natural Science Foundation of China （31270936 and 81261120380） and Shanghai Municipal Government （12XD 1405800）.

摘　　要：RAG1 and RAG2 proteins are key components in V（D）J recombination. The core region of RAG1 is capable of catalyzing the recombination reaction; however, the biological function of non-core RAG1 remains largely unknown. Here, we show that in a murine-model carrying the RAG1 ring-finger conserved cysteine residue mutation （C325Y）, V（D）J recombination was abrogated at the cleavage step, and this effect was accompanied by decreased mono-ubiquitylation of histone H3. Further analyses suggest that un-ubiquitylated histone H3 restrains RAG1 to the chromatin by interacting with the N-terminal 218 amino acids of RAG1. Our data provide evidence for a model in which ubiquitylation of histone H3 mediated by the ring-finger domain of RAG1 triggers the release of RAG1, thus allowing its transition into the cleavage phase. Collectively, our findings reveal that the non-core region of RAG1 facilitates chromosomal V（D）J recombination in a ubiquitylation-dependent pathway.

关 键 词：RAG 1 UBIQUITYLATION V（D）J recombination histone H3 

分 类 号：Q26[生物学—细胞生物学] S511[农业科学—作物学]