Journal Article

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

Zimu Deng Haifeng Liu Xiaolong Liu

2015

Overview

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.

• Subject: 介导 / 半胱氨酸残基 / 小鼠模型 / 染色体 / 泛素化 / 生物学功能 / 组蛋白H3 / 重组反应