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

• 成果类型: Article
• 署名作者: Liu, Guangxue; Huang, Kaiyan; Liu, Shiyao; Xie, Yali; Huang, Jinyan; Liang, Tingbo; Zhang, Pumin
• 署名单位: Zhejiang University; Zhejiang University; Zhejiang University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10624
• DOI: 10.1073/pnas.2410119121
• 发表日期: 2024-12-10
• 关键词: dnmt1; protein; overexpression

摘要

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 and degradation of the DNA methyltransferase DNMT1, leading to the loss of global DNA methylation. Second, RAD51 helps UHRF1 to monoubiquitinate histone H3 H3 diminishes DNMT1 recruitment and the failure of maintenance methylation of as a guardian of the integrity of both the genome and the epigenome.