HMCES Proteins

Protein Information

Sensor of abasic sites in single-stranded DNA (ssDNA) required to preserve genome integrity by promoting error-free repair of abasic sites (PubMed:30554877, PubMed:31235915, PubMed:31235913). Acts as an enzyme that recognizes and binds abasic sites in ssDNA at replication forks and chemically modifies the lesion by forming a covalent cross-link with DNA: forms a stable thiazolidine linkage between a ring-opened abasic site and the alpha-amino and sulfhydryl substituents of its N-terminal catalytic cysteine residue (PubMed:30554877, PubMed:31235913). The HMCES DNA-protein cross-link is then degraded by the proteasome (PubMed:30554877). Promotes error-free repair of abasic sites by acting as a 'suicide' enzyme that is degraded, thereby protecting abasic sites from translesion synthesis (TLS) polymerases and endonucleases that are error-prone and would generate mutations and double-strand breaks (PubMed:30554877). Has preference for ssDNA, but can also accommodate double-stranded DNA with 3' or 5' overhang (dsDNA), and dsDNA-ssDNA 3' junction (PubMed:31235915, PubMed:31806351). Also involved in class switch recombination (CSR) in B-cells independently of the formation of a DNA-protein cross-link: acts by binding and protecting ssDNA overhangs to promote DNA double-strand break repair through the microhomology-mediated alternative-end-joining (Alt-EJ) pathway. Acts as a protease: mediates autocatalytic processing of its N-terminal methionine in order to expose the catalytic cysteine. [UniProt]

Synonyms

5-hydroxymethylcytosine (hmC) binding, ES cell specific; 5-hydroxymethylcytosine (hmC) binding, ES cell-specific; 8430410A17Rik; Abasic site processing protein HMCES; C3orf37; C85376; DC12; Embryonic stem cell-specific 5-hydroxymethylcytosine-binding protein; ES cell-specific 5hmC-binding protein; Hmces; Peptidase HMCES; Putative endonuclease HMCES; putative peptidase SRAPD1; SRAP domain-containing protein 1; Srap1; SRAPD1; UPF0361 protein C3orf37; UPF0361 protein C3orf37 homolog