{"doi":"10.1073/pnas.2528670122","title":"DNA mismatch repair mediated by Mlh1–Pms1 endonuclease-catalyzed mispair excision","abstract":"Eukaryotic DNA mismatch repair (MMR) involves several excision pathways, including those mediated by exonuclease 1 (Exo1) and by the flap endonuclease Rad27 (human FEN1) coupled with DNA polymerase δ. Simultaneous inactivation of both excision mechanisms causes an MMR defect that is at most 5 to 13% of that caused by complete inactivation of MMR. Here, we reconstituted nicked-strand-specific MMR with the Saccharomyces cerevisiae proteins Msh2-Msh6 or Msh2-Msh3, DNA polymerase ε, RFC, PCNA, RPA, and Mlh1-Pms1 (human Mlh1-Pms2) under conditions lacking Exo1, Rad27, or strand-displacement synthesis by DNA polymerase δ. These reactions required the Mlh1-Pms1 endonuclease activity, its activation by RFC and PCNA, and its recruitment by Msh2-Msh6 or Msh2-Msh3. MMR was mediated by nicked-strand-specific excision by Mlh1-Pms1 through formation of single-strand DNA gaps having a broad range of sizes. This reaction is consistent with genetic data demonstrating redundancy between the Exo1, Rad27, and Mlh1-Pms1 excision pathways in MMR.","journal":"Proceedings of the National Academy of Sciences","year":2025,"id":586925,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":707436,"name":"Felipe A. Calil","orcid":"0000-0001-7503-4078","position":1,"is_corresponding":false},{"id":708146,"name":"Nikki Bowen","orcid":null,"position":2,"is_corresponding":false},{"id":1502069,"name":"J Griffith","orcid":null,"position":3,"is_corresponding":false},{"id":280627,"name":"Christopher D. Putnam","orcid":"0000-0002-6145-1265","position":4,"is_corresponding":false},{"id":247631,"name":"Richard D. Kolodner","orcid":"0000-0002-4806-8384","position":5,"is_corresponding":false},{"id":921097,"name":"Tatiana Palacio","orcid":null,"position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:59:32.191237Z","pmid":"41439704","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":[]}