AMPK-mediated phosphorylation on 53BP1 promotes c-NHEJ

AMP-activated protein kinase (AMPK) is an energy sensor that plays roles in multiple biological processes beyond metabolism. Several studies have suggested that AMPK is involved in the DNA damage response (DDR), but the mechanisms remain unclear. Herein, we demonstrate that AMPK promotes classic non...

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Published in:Cell reports (Cambridge) 2021-02, Vol.34 (7), p.108713-108713, Article 108713
Main Authors: Jiang, Yuejing, Dong, Ying, Luo, Yifeng, Jiang, Shangwen, Meng, Fei-Long, Tan, Minjia, Li, Jia, Zang, Yi
Format: Article
Language:English
Subjects:
53BP1
AMP-Activated Protein Kinases - metabolism
AMPK
DNA double-strand break repair
DNA End-Joining Repair
Genomic Instability
genomic stability
Humans
Phosphorylation
Tumor Suppressor p53-Binding Protein 1 - metabolism
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Summary:AMP-activated protein kinase (AMPK) is an energy sensor that plays roles in multiple biological processes beyond metabolism. Several studies have suggested that AMPK is involved in the DNA damage response (DDR), but the mechanisms remain unclear. Herein, we demonstrate that AMPK promotes classic non-homologous end joining (c-NHEJ) in double-strand break (DSB) repair through 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 the interaction of AMPK and 53BP1 spatially occurs under DSB stress. In the context of DSBs, AMPK directly phosphorylates 53BP1 at Ser1317 and promotes 53BP1 recruitment during DDR for an efficient c-NHEJ, thus maintaining genomic stability and diversity of the immune repertoire. Taken together, our study demonstrates that AMPK is a regulator of 53BP1 and controls c-NHEJ choice by phospho-regulation. [Display omitted] •AMPK promotes c-NHEJ in DSB repair•AMPK phosphorylates 53BP1 at the S1317 site to promote 53BP1 recruitment•AMPK-mediated Ser1317 phosphorylation promotes 53BP1-dependent c-NHEJ activity Jiang et al. show that AMPK phosphorylates 53BP1 at Ser1317 to promote 53BP1 recruitment and classic non-homologous end joining (c-NHEJ) activity in double-strand break (DSB) repair. The phosphorylation of Ser1317 is essential for the maintenance of genomic stability and diversity of the immune repertoire.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2021.108713