{"doi":"10.1126/sciadv.abl6083","title":"Integrated -omics approach reveals persistent DNA damage rewires lipid metabolism and histone hyperacetylation via MYS-1/Tip60","abstract":"Although DNA damage is intricately linked to metabolism, the metabolic alterations that occur in response to DNA damage are not well understood. We use a DNA repair–deficient model of ERCC1-XPF in Caenorhabditis elegans to gain insights on how genotoxic stress drives aging. Using multi-omic approach, we discover that nuclear DNA damage promotes mitochondrial β-oxidation and drives a global loss of fat depots. This metabolic shift to β-oxidation generates acetyl–coenzyme A to promote histone hyperacetylation and an associated change in expression of immune-effector and cytochrome genes. We identify the histone acetyltransferase MYS-1, as a critical regulator of this metabolic-epigenetic axis. We show that in response to DNA damage, polyunsaturated fatty acids, especially arachidonic acid (AA) and AA-related lipid mediators, are elevated and this is dependent on mys-1 . Together, these findings reveal that DNA damage alters the metabolic-epigenetic axis to drive an immune-like response that can promote age-associated decline.","journal":"Science Advances","year":2022,"id":248375,"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":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9462,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":110050,"name":"Tamil S. Anthonymuthu","orcid":"0000-0002-3460-5003","position":1,"is_corresponding":false},{"id":820799,"name":"Suhao Han","orcid":"0000-0001-6013-9467","position":2,"is_corresponding":false},{"id":820800,"name":"Himaly Shinglot","orcid":"0000-0001-7726-8417","position":3,"is_corresponding":false},{"id":820801,"name":"Ella Siefken","orcid":"0000-0002-9931-248X","position":4,"is_corresponding":false},{"id":820802,"name":"Austin Sims","orcid":"0000-0002-1509-8421","position":5,"is_corresponding":false},{"id":275721,"name":"Payel Sen","orcid":"0000-0003-2809-0901","position":6,"is_corresponding":false},{"id":563070,"name":"Hannah L. Pepper","orcid":"0000-0001-8931-7706","position":7,"is_corresponding":false},{"id":237765,"name":"Nathaniel W. Snyder","orcid":"0000-0001-5643-8747","position":8,"is_corresponding":false},{"id":110070,"name":"Hülya Bayır","orcid":"0000-0003-2361-4120","position":9,"is_corresponding":false},{"id":110071,"name":"Valerian E. Kagan","orcid":"0000-0002-7245-1885","position":10,"is_corresponding":false},{"id":233164,"name":"Aditi U. Gurkar","orcid":"0000-0003-4338-0624","position":11,"is_corresponding":false},{"id":820798,"name":"Shruthi Hamsanathan","orcid":"0000-0002-6613-180X","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T00:24:09.893688Z","pmid":"35171671","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":[]}