AMPK-Mediated Phosphorylation on 53BP1 Promotes NHEJ

AMP-activated protein kinase (AMPK) is an energy sensor that plays roles in basic biological processes. Several studies have shed light on the regulatory role of AMPK in DNA damage response (DDR), but the mechanisms remain unclear. Herein, we demonstrate that AMPK promotes non-homologous end-joining (NHEJ) in double-strand break (DSB) repair including programmed end-joining of antibody class switch recombination (CSR), via recruiting a key chromatin-based mediator named p53-binding protein 1 (53BP1) which facilitates the end-joining of distal DNA ends during DDR. We find that AMPK interacts with 53BP1 in a DSB-dependent manner. Upon DSB,the kinase phosphorylates 53BP1 at Ser1317, as demonstrated by in vitro and in vivo assays and promotes 53BP1 recruitment, thus promoting to chromatin breaks for an efficient DSB repair via NHEJ and maintenance of genomic stability. Overall, our study indicates that the AMPK-53BP1 axis contributes to genomic integrity by promoting NHEJ activity.