RAD51 plays critical roles in DNMT1-mediated maintenance methylation of genomic DNA by dually regulating the ubiquitin ligase UHRF1

IF 9.4 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2024-12-02 DOI:10.1073/pnas.2410119121

Guangxue Liu, Kaiyan Huang, Shiyao Liu, Yali Xie, Jinyan Huang, Tingbo Liang, Pumin Zhang

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引用次数: 0

Abstract

RAD51 is related to the bacterial RecA protein and is best known for its role in homologous recombination-mediated repair of DNA damage. Here, we report an unexpected function of RAD51 in the maintenance methylation of genomic DNA, a function that is separable from its role in homologous recombination. First, it acts as an inhibitor of the E3 ubiquitin ligase UHRF1. Deficiency in RAD51 causes excessive ubiquitination and degradation of the DNA methyltransferase DNMT1, leading to the loss of global DNA methylation. Second, RAD51 helps UHRF1 to monoubiquitinate histone H3 to generate DNMT1 recruiting signal. It binds H3 directly, enabling UHRF1 to bind and ubiquitinate H3 more readily. Disrupting the interaction between RAD51 and H3 diminishes DNMT1 recruitment and the failure of maintenance methylation of genomic DNA. Thus, RAD51 dually regulates UHRF1. These results establish RAD51 as a guardian of the integrity of both the genome and the epigenome.

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来源期刊

Proceedings of the National Academy of Sciences of the United States of America 综合性期刊-综合性期刊

CiteScore

19.00

自引率

0.90%

发文量

3575

审稿时长

2.5 months

期刊介绍： The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.