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

• DOI: 10.1073/pnas.2410119121
• Publication Date: 2024-12-02T20:10:12Z
• Authors: Guangxue Liu; Kaiyan Huang; Shiyao Liu; Yali Xie; Jinyan Huang; Tingbo Liang; Pumin Zhang
• Keywords: DNMT1

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