{"doi":"10.1101/2023.10.23.563644","title":"Genome Editing Outcomes Reveal Mycobacterial NucS Participates in a Short-Patch Repair of DNA Mismatches","abstract":"SUMMARY In the canonical DNA mismatch repair (MMR) mechanism in bacteria, if during replication a nucleotide is incorrectly mis-paired with the template strand, 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, which has led to the idea that NucS might be involved in a cryptic, independently-evolved DNA MMR mechanism. It has been proposed that nuclease activity at a mismatch might result in correction by homologous recombination (HR) with a sister chromatid. Using oligonucleotide recombination, which allows us to introduce mismatches during replication 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":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":395266,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"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":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":52,"raw_metadata":null,"created_at":"2026-07-19T01:19:18.686170Z","pmid":"37961639","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":[]}