{"doi":"10.1016/j.celrep.2023.113427","title":"Self-reversal facilitates the resolution of HMCES DNA-protein crosslinks in cells","abstract":"Abasic sites are common DNA lesions stalling polymerases and threatening genome stability. When located in single-stranded DNA (ssDNA), they are shielded from aberrant processing by 5-hydroxymethyl cytosine, embryonic stem cell (ESC)-specific (HMCES) via a DNA-protein crosslink (DPC) that prevents double-strand breaks. Nevertheless, HMCES-DPCs must be removed to complete DNA repair. Here, we find that DNA polymerase α inhibition generates ssDNA abasic sites and HMCES-DPCs. These DPCs are resolved with a half-life of approximately 1.5 h. HMCES can catalyze its own DPC self-reversal reaction, which is dependent on glutamate 127 and is favored when the ssDNA is converted to duplex DNA. When the self-reversal mechanism is inactivated in cells, HMCES-DPC removal is delayed, cell proliferation is slowed, and cells become hypersensitive to DNA damage agents that increase AP (apurinic/apyrimidinic) site formation. In these circumstances, proteolysis may become an important mechanism of HMCES-DPC resolution. Thus, HMCES-DPC formation followed by self-reversal is an important mechanism for ssDNA AP site management.","journal":"Cell Reports","year":2023,"id":335704,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":302102,"name":"Courtney A. Lovejoy","orcid":"0000-0001-9178-5226","position":1,"is_corresponding":false},{"id":302101,"name":"Kavi P.M. Mehta","orcid":"0000-0002-2582-073X","position":2,"is_corresponding":false},{"id":908218,"name":"Katherine A. Paulin","orcid":"0000-0002-9311-9136","position":3,"is_corresponding":false},{"id":1066192,"name":"Yasmine T. Toudji","orcid":null,"position":4,"is_corresponding":false},{"id":1052200,"name":"Celeste Giansanti","orcid":"0000-0003-3229-8385","position":5,"is_corresponding":false},{"id":246977,"name":"Brandt F. Eichman","orcid":"0000-0002-0965-2297","position":6,"is_corresponding":false},{"id":252498,"name":"David Cortez","orcid":"0000-0003-0154-140X","position":7,"is_corresponding":false},{"id":1066191,"name":"Jorge Rua-Fernandez","orcid":null,"position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T01:10:02.777338Z","pmid":"37950866","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}