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5-HYDROXYMETHYLCYTOSINE-BINDING PROTEIN, EMBRYONIC STEM CELL-SPECIFIC; HMCES

5-HYDROXYMETHYLCYTOSINE-BINDING PROTEIN, EMBRYONIC STEM CELL-SPECIFIC; HMCES

HGNC Approved Gene Symbol: HMCESCytogenetic location: 3q21.3 Genomic coordinates (GRCh38): 3:129,278,831-129,306,185 (from NCBI)▼ DescriptionHMCES is a DNA d...

HGNC Approved Gene Symbol: HMCES

Cytogenetic location: 3q21.3 Genomic coordinates (GRCh38): 3:129,278,831-129,306,185 (from NCBI)

▼ Description
HMCES is a DNA damage recognition protein that preserves genome integrity by facilitating repair of abasic sites (AP sites) in single-stranded DNA (ssDNA) (Mohni et al., 2019).

▼ Cloning and Expression
Mohni et al. (2019) reported that human HMCES contains 354 amino acids and includes a SRAP domain and a C-terminal PCNA (176740)-interacting peptide (PIP) box. Localization and immunoblot analyses in various human cell lines showed that HMCES was expressed at higher levels in S-phase cells than quiescent cells and localized at replication forks. HMCES is present in almost all organisms in every domain of life and in several viruses.

▼ Gene Function
Mohni et al. (2019) found that human HMCES bound to ssDNA and PCNA to form a covalently linked DNA-protein complex at replication forks. Analysis with HMCES-deficient or -overexpressing cells showed that HMCES did not regulate gene expression or epigenetic marks, but instead functioned as a replication stress response protein, as HMCES inactivation caused slower doubling times with elevated DNA damage to cells. Further analysis demonstrated that HMCES sensed AP sites and shielded them from endonucleases and translesion synthesis polymerases by forming a DNA-protein crosslink (DPC) with ssDNA to facilitate error-free repair, thereby maintaining genome stability during DNA replication. Examination of HMCES responses to DNA oxidative damage revealed that the DPC formed by HMCES was an intermediate and that HMCES was degraded through ubiquitin-mediated proteolysis.

▼ Mapping
Gross (2019) mapped the HMCES gene to chromosome 3q21.3 based on an alignment of the HMCES sequence (GenBank AF201934) with the genomic sequence (GRCh38).

Tags: 3q21.3