Structural highlights
Function
HMCES_HUMAN Specifically binds 5-hydroxymethylcytosine (5hmC)-containing DNA in stem cells, suggesting that it acts as a specific reader of 5hmC in stem cells (By similarity). May act as a peptidase; experimental evidences are however required to confirm this prediction (PubMed:23945014).[1]
Publication Abstract from PubMed
Embryonic stem cell-specific 5-hydroxymethylcytosine-binding protein (HMCES) can covalently cross-link to abasic sites in single-stranded DNA at stalled replication forks to prevent genome instability. Here, we report crystal structures of the human HMCES SOS response-associated peptidase (SRAP) domain in complex with DNA-damage substrates, including HMCES cross-linked with an abasic site within a 3' overhang DNA. HMCES interacts with both single-strand and duplex segments of DNA, with two independent duplex DNA interaction sites identified in the SRAP domain. The HMCES DNA-protein cross-link structure provides structural insights into a novel thiazolidine covalent interaction between the DNA abasic site and conserved Cys 2 of HMCES. Collectively, our structures demonstrate the capacity for the SRAP domain to interact with a variety of single-strand- and double-strand-containing DNA structures found in DNA-damage sites, including 5' and 3' overhang DNAs and gapped DNAs with short single-strand segments.
Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition.,Halabelian L, Ravichandran M, Li Y, Zeng H, Rao A, Aravind L, Arrowsmith CH Nat Struct Mol Biol. 2019 Jul;26(7):607-612. doi: 10.1038/s41594-019-0246-6. Epub, 2019 Jun 24. PMID:31235913[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Aravind L, Anand S, Iyer LM. Novel autoproteolytic and DNA-damage sensing components in the bacterial SOS response and oxidized methylcytosine-induced eukaryotic DNA demethylation systems. Biol Direct. 2013 Aug 15;8:20. doi: 10.1186/1745-6150-8-20. PMID:23945014 doi:http://dx.doi.org/10.1186/1745-6150-8-20
- ↑ Halabelian L, Ravichandran M, Li Y, Zeng H, Rao A, Aravind L, Arrowsmith CH. Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition. Nat Struct Mol Biol. 2019 Jul;26(7):607-612. doi: 10.1038/s41594-019-0246-6. Epub, 2019 Jun 24. PMID:31235913 doi:http://dx.doi.org/10.1038/s41594-019-0246-6
