PCAF-mediated acetylation regulates RAD51 dynamic localization on chromatin during HR repair.

ABSTRACT: PCAF (p300-associated factor), a major histone acetyltransferase, is involved in many metabolic and pathogenic diseases. Here, we reveal a novel function of PCAF in homologous recombination repair (HR). We demonstrate that RAD51, a core protein in HR repair, physically interacts with the acetyltransferase domain of PCAF and is acetylated at lysine 40. This acetylation promotes RAD51 binding to ubiquitin, leading to its degradation via the ubiquitin-proteasome pathway. Following etoposide treatment, PCAF-induced acetylation removes RAD51 from chromatin to facilitate the late-phase HR processes. Overexpression of PCAF promotes premature dissociation of RAD51 from DNA damage sites. Notably, PCAF is downregulated in many cancers compared to adjacent tissues, correlating with shortened patient

SUBMITTER: Hou J 

PROVIDER: S-EPMC12373954 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature