{"doi":"10.1093/nar/gkae402","title":"Genome editing outcomes reveal mycobacterial NucS participates in a short-patch repair of DNA mismatches","abstract":"In the canonical DNA mismatch repair (MMR) mechanism in bacteria, if a nucleotide is incorrectly mis-paired with the template strand during replication, the resulting repair of this mis-pair can result in the degradation and re-synthesis of hundreds or thousands of nucleotides on the newly-replicated strand (long-patch repair). While mycobacteria, which include important pathogens such as Mycobacterium tuberculosis, lack the otherwise highly-conserved enzymes required for the canonical MMR reaction, it was found that disruption of a mycobacterial mismatch-sensitive endonuclease NucS results in a hyper-mutative phenotype, leading to the idea that NucS might be involved in a cryptic, independently-evolved DNA MMR mechanism, perhaps mediated by homologous recombination (HR) with a sister chromatid. Using oligonucleotide recombination, which allows us to introduce mismatches specifically into the genomes of a model for M. tuberculosis, Mycobacterium smegmatis, we find that NucS participates in a direct repair of DNA mismatches where the patch of excised nucleotides is largely confined to within ∼5-6 bp of the mis-paired nucleotides, which is inconsistent with mechanistic models of canonical mycobacterial HR or other double-strand break (DSB) repair reactions. The results presented provide evidence of a novel NucS-associated mycobacterial MMR mechanism occurring in vivo to regulate genetic mutations in mycobacteria.","journal":"Nucleic Acids Research","year":2024,"id":454509,"datarank":0.40976600524466616,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.09784977399269075,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.09784977399269075,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":7,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":true,"deposit_databanks":{"BioProject":["PRJNA1105094"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":924833,"name":"Eric A. Josephs","orcid":"0000-0002-5330-6842","position":1,"is_corresponding":false},{"id":1170558,"name":"Tanjina Islam","orcid":null,"position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T02:03:12.720997Z","pmid":"38747340","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":[]}