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Keywords:

  • ATM;
  • KAP-1;
  • chromatin remodeling;
  • DNA repair;
  • Zmpste24;
  • cellular senescence;
  • progeria

Summary

ATM-mediated phosphorylation of KAP-1 triggers chromatin remodeling and facilitates the loading and retention of repair proteins at DNA lesions. Mouse embryonic fibroblasts (MEFs) derived from Zmpste24−/− mice undergo early senescence, attributable to delayed recruitment of DNA repair proteins. Here, we show that ATM-Kap-1 signaling is compromised in Zmpste24−/− MEFs, leading to defective DNA damage-induced chromatin remodeling. Knocking down Kap-1 rescues impaired chromatin remodeling, defective DNA repair and early senescence in Zmpste24−/− MEFs. Thus, ATM-Kap-1-mediated chromatin remodeling plays a critical role in premature aging, carrying significant implications for progeria therapy.