HDGFRP3 interaction with 53BP1 promotes DNA double-strand break repair.

ABSTRACT: The 53BP1-dependent end-joining pathway plays a critical role in double-strand break (DSB) repair. However, the regulators of 53BP1 in chromatin remain incompletely characterized. In this study, we identified HDGFRP3 (hepatoma-derived growth factor related protein 3) as a 53BP1-interacting protein. The HDGFRP3-53BP1 interaction is mediated by the PWWP domain of HDGFRP3 and the Tudor domain of 53BP1. Importantly, we observed that the HDGFRP3-53BP1 complex co-localizes with 53BP1 or γH2AX at sites of DSB and participates in the response to DNA damage repair. Loss of HDGFRP3 impairs classical non-homologous end-joining repair (NHEJ), curtails the accumulation of 53BP1 at DSB sites, and enhances DNA end-resection. Moreover, the HDGFRP3-53BP1 interaction is required for cNHEJ repair, 53BP1 recr

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC10018360 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature