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Lactylation, a newly identified post-translational modification, plays a key role in tumorigenesis and cancer progression. Herein, we discovered that XPA was lactylated in the DNA-binding domain by the acyl-transferase KAT5. In addition, UV irradiation promoted XPA lactylation, thereby increasing the chromatin recruitment of XPA and NER. However, the mutation of XPA to a lactylation-deficient form impeded XPA chromatin recruitment under UV irradiation, impaired NER, and rendered cancer cells hypersensitive to UV irradiation. Our data demonstrate that the lactylation of XPA plays a crucial role in NER and reveals the link between metabolic reprogramming and DNA damage repair induced by UV irradiation.<\/jats:p>","DOI":"10.1093\/nar\/gkag947","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:38:11Z","timestamp":1790077091000},"source":"Crossref","is-referenced-by-count":0,"title":["XPA lactylation is required for UV-induced DNA damage repair"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3047-9051","authenticated-orcid":false,"given":"Jie","family":"Yang","sequence":"first","affiliation":[{"name":"Jiangxi Provincial Key Laboratory of Respiratory Diseases; Jiangxi Institute of Respiratory Diseases; Jiangxi Clinical Research Center for Respiratory Diseases; Department of Thoracic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University , Nanchang 330006 ,","place":["China"]},{"name":"China-Japan 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