{"doi":"10.1038/s41467-024-50006-8","title":"Obesity increases genomic instability at DNA repeat-mediated endogenous mutation hotspots","abstract":"Obesity is associated with increased cancer risk, yet the underlying mechanisms remain elusive. Obesity-associated cancers involve disruptions in metabolic and cellular pathways, which can lead to genomic instability. Repetitive DNA sequences capable of adopting alternative DNA structures (e.g., H-DNA) stimulate mutations and are enriched at mutation hotspots in human cancer genomes. However, it is not known if obesity impacts DNA repeat-mediated endogenous mutation hotspots. We address this gap by measuring mutation frequencies in obese and normal-weight transgenic reporter mice carrying either a control human B-DNA- or an H-DNA-forming sequence (from a translocation hotspot in c-MYC in Burkitt lymphoma). Here, we discover that H-DNA-induced DNA damage and mutations are elevated in a tissue-specific manner, and DNA repair efficiency is reduced in obese mice compared to those on the control diet. These findings elucidate the impact of obesity on cancer-associated endogenous mutation hotspots, providing mechanistic insight into the link between obesity and cancer.","journal":"Nature Communications","year":2024,"id":430443,"datarank":0.5945139944726288,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.1451541534395301,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.1451541534395301,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":16,"citers_with_citation_signal":11,"citers_with_endowment":11,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":true,"deposit_databanks":{"figshare":["23820834"]},"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":294120,"name":"Guliang Wang","orcid":"0000-0001-6871-7540","position":1,"is_corresponding":false},{"id":394099,"name":"R. Durrett","orcid":null,"position":2,"is_corresponding":false},{"id":1233456,"name":"Yating Lai","orcid":"0000-0002-8903-069X","position":3,"is_corresponding":false},{"id":1233778,"name":"Celeste Marin","orcid":null,"position":4,"is_corresponding":false},{"id":484953,"name":"Yuan Liu","orcid":"0000-0003-4797-6396","position":5,"is_corresponding":false},{"id":933669,"name":"Samy L. Habib","orcid":"0000-0002-6655-3180","position":6,"is_corresponding":false},{"id":348917,"name":"John DiGiovanni","orcid":"0000-0003-4233-6728","position":7,"is_corresponding":false},{"id":294124,"name":"Karen M. Vásquez","orcid":"0000-0002-6958-5073","position":8,"is_corresponding":false},{"id":1233455,"name":"Pallavi Kompella","orcid":"0000-0002-9508-5603","position":0,"is_corresponding":true}],"reference_count":96,"raw_metadata":null,"created_at":"2026-07-19T01:59:16.092672Z","pmid":"39043652","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":[]}