HMCES corrupts replication fork stability during base excision repair in homologous recombination-deficient cells.

ABSTRACT: Apurinic/apyrimidinic (AP) sites and single-strand breaks arising from base excision repair (BER) during the misincorporation of damaged nucleobases may hinder replication fork stability in homologous recombination-deficient (HRD) cells. At templated AP sites, cross-links between the DNA and 5-hydroxymethylcytosine binding, embryonic stem cell-specific (HMCES) regulate replication fork speed, avoiding cytotoxic double-strand breaks. While the role of HMCES at the template DNA strand is well studied, its effects on nascent DNA are not. We provide evidence that HMCES-DNA-protein cross-links (DPCs) are detrimental to the BER-mediated removal of 5-hydroxymethyl-2'-deoxycytidine (5hmdC)-derived 5-hydroxymethyl-2'-deoxyuridine from replication forks. HRD cells have heightened HMCES-DPCs, which i

SUBMITTER: Pena-Gomez MJ 

PROVIDER: S-EPMC11939059 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature