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However, the role of STAG2 in DNA repair and its therapeutic implications are largely unknown. Here it is reported that knockout of STAG2 results in increased double\u2010stranded breaks (DSBs) and chromosomal aberrations by reducing homologous recombination (HR) repair, and confers hypersensitivity to inhibitors of ataxia telangiectasia mutated (ATMi), Poly ADP Ribose Polymerase (PARPi), or the combination of both. Of note, the impaired HR by STAG2\u2010deficiency is mainly attributed to the restored expression of KMT5A, which in turn methylates H4K20 (H4K20me0) to H4K20me1 and thereby decreases the recruitment of BRCA1\u2010BARD1 to chromatin. Importantly, STAG2 expression correlates with poor prognosis of cancer patients. STAG2 is identified as an important regulator of HR and a potential therapeutic strategy for STAG2\u2010mutant tumors is elucidated.<\/jats:p>","DOI":"10.1002\/advs.202302494","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T17:56:05Z","timestamp":1700589365000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["STAG2 Regulates Homologous Recombination Repair and Sensitivity to ATM Inhibition"],"prefix":"10.1002","volume":"10","author":[{"given":"Jie","family":"Zhou","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou 510060 China"},{"name":"Guangxi International Travel Healthcare Centre (Port Clinic of Nanning Customs District)  Nanning Guangxi 530021 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