{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Halabelian L"],"funding":["NCRR NIH HHS","NIAID NIH HHS","NCI NIH HHS","Wellcome Trust","NIGMS NIH HHS","NIH HHS"],"pagination":["607-612"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6609482"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(7)"],"pubmed_abstract":["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."],"journal":["Nature structural & molecular biology"],"pubmed_title":["Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition."],"pmcid":["PMC6609482"],"funding_grant_id":["R35 CA210043","R37 CA042471","S10 RR029205","R01 AI040127","P41 GM103403","R01 CA151535","S10 OD021832"],"pubmed_authors":["Rao A","Li Y","Halabelian L","Arrowsmith CH","Ravichandran M","Zeng H","Aravind L"],"additional_accession":[]},"is_claimable":false,"name":"Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition.","description":"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.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jul","modification":"2024-11-13T06:49:17.538Z","creation":"2020-05-22T00:07:24Z"},"accession":"S-EPMC6609482","cross_references":{"pubmed":["31235913"],"doi":["10.1038/s41594-019-0246-6"]}}