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Adv."],"published-print":{"date-parts":[[2026,9,11]]},"abstract":"<jats:p>\n                    Accurate repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is essential for genome stability. Nuclear production of acetyl\u2013coenzyme A (acetyl-CoA) by ATP\u2013citrate lyase (ACLY) promotes HR, yet how ACLY is regulated during the DNA damage response (DDR) remains unclear. Here, we identify a phosphorylation-dependent signaling axis in which glycogen synthase kinase 3\u03b2 (GSK3\u03b2) and Polo-like kinase 1 (Plk1) act sequentially on ACLY to facilitate HR-mediated repair of DSBs induced by ionizing radiation. Following AKT-dependent phosphorylation of ACLY at Ser\n                    <jats:sup>455<\/jats:sup>\n                    , GSK3\u03b2 phosphorylates ACLY at Thr\n                    <jats:sup>447<\/jats:sup>\n                    , generating a docking site for Plk1, which in turn phosphorylates ACLY at Ser\n                    <jats:sup>442<\/jats:sup>\n                    . This phosphorylation cascade, enhanced by radiation, sustains histone acetylation, supports the accumulation of BRCA1 and RAD51 at DSBs, and confers cellular resistance to poly(ADP-ribose) polymerase (PARP) inhibition. Together, our findings define an AKT-GSK3\u03b2-Plk1-ACLY signaling module that links the DDR to nuclear metabolism, revealing a critical mechanism by which kinase signaling facilitates acetyl-CoA\u2013dependent chromatin remodeling to preserve genome integrity.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeg1097","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:58:47Z","timestamp":1788976727000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["GSK3\u03b2 and Plk1 sequentially phosphorylate ATP\u2013citrate lyase to promote homologous recombination"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1238-0441","authenticated-orcid":true,"given":"Shinan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Gynecologic Oncology, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou, 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