{"doi":"10.17615/m0g4-dr84","title":"Clustered Mutations in Yeast and in Human Cancers Can Arise from Damaged Long Single-Strand DNA Regions","abstract":"Mutations are typically perceived as random, independent events. We describe here non-random clustered mutations in yeast and in human cancers. Genome sequencing of yeast grown under chronic alkylation damage identified mutation clusters that extend up to 200 kb. A predominance of “strand-coordinated” changes of either cytosines or guanines in the same strand, mutation patterns and genetic controls indicated that simultaneous mutations were generated by base alkylation in abnormally long single-strand (ss)DNA formed at double-strand breaks (DSBs) and replication forks. Significantly, we found mutation clusters with analogous features in sequenced human cancers. Strand-coordinated clusters of mutated cytosines or guanines often resided near chromosome rearrangement breakpoints and were highly enriched with a motif targeted by APOBEC family cytosine-deaminases, which strongly prefer ssDNA. These data indicate that hyper-mutation via multiple simultaneous changes in randomly formed ssDNA is a general phenomenon that may be an important mechanism producing rapid genetic variation.","journal":"UNC Libraries","year":2020,"id":136983,"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":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":13498,"name":"Dmitry A. Gordenin","orcid":"0000-0002-8399-1836","position":1,"is_corresponding":false},{"id":108245,"name":"Ewa P. Malc","orcid":"0000-0002-4596-1142","position":2,"is_corresponding":false},{"id":297213,"name":"Deepak Mav","orcid":"0000-0002-4683-7813","position":3,"is_corresponding":false},{"id":299843,"name":"Ruchir Shah","orcid":null,"position":4,"is_corresponding":false},{"id":418508,"name":"Joan F. Sterling","orcid":"0000-0003-0920-4694","position":5,"is_corresponding":false},{"id":13808,"name":"Piotr A. Mieczkowski","orcid":"0000-0003-2418-0096","position":6,"is_corresponding":false},{"id":531790,"name":"Shawn Harris","orcid":"0000-0003-3169-9128","position":7,"is_corresponding":false},{"id":13970,"name":"Steven A. Roberts","orcid":"0000-0002-3628-5808","position":8,"is_corresponding":false},{"id":546786,"name":"Michael A. Resnick","orcid":"0000-0002-8473-7506","position":9,"is_corresponding":false},{"id":596180,"name":"Cole Thompson","orcid":"0000-0001-5184-9459","position":10,"is_corresponding":false},{"id":18774,"name":"Gregory V. Kryukov","orcid":"0000-0002-6131-9483","position":11,"is_corresponding":false},{"id":13666,"name":"Leszek J. Klimczak","orcid":"0000-0003-3048-2576","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:52.487376Z","pmid":null,"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":[]}