HMCES

HMCES (5-Hydroxymethylcytosine Binding, ES Cell Specific) is a Protein Coding gene. Gene Ontology (GO) annotations related to this gene include peptidase activity.

Full Name

5-Hydroxymethylcytosine Binding, ES Cell Specific

Function

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 (By similarity).

Acts as a protease: mediates autocatalytic processing of its N-terminal methionine in order to expose the catalytic cysteine (By similarity).

Biological Process

Cellular response to DNA damage stimulus Source: UniProtKB
Double-strand break repair via alternative nonhomologous end joining Source: Ensembl
Positive regulation of isotype switching Source: UniProtKB
Protein-DNA covalent cross-linking Source: UniProtKB

Cellular Location

Chromosome. Recruited to chromatin following DNA damage (PubMed:30554877). Localizes to replication forks (PubMed:30554877).

PTM

Ubiquitinated; the covalent HMCES DNA-protein cross-link is ubiquitinated, leading to its degradation by the proteasome.