Regulation of DNA double-strand break repair pathway choice: a new focus on 53BP1.

Fan Zhang, Zihua Gong

Journal of Zhejiang University. Science. B 2021 Jan 15

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Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break (DSB) signaling. P53-binding protein 1 (53BP1) plays a critical role in coordinating the DSB repair pathway choice and promotes the non-homologous end-joining (NHEJ)-mediated DSB repair pathway that rejoins DSB ends. New insights have been gained into a basic molecular mechanism that is involved in 53BP1 recruitment to the DNA lesion and how 53BP1 then recruits the DNA break-responsive effectors that promote NHEJ-mediated DSB repair while inhibiting homologous recombination (HR) signaling. This review focuses on the up- and downstream pathways of 53BP1 and how 53BP1 promotes NHEJ-mediated DSB repair, which in turn promotes the sensitivity of poly(ADP-ribose) polymerase inhibitor (PARPi) in BRCA1-deficient cancers and consequently provides an avenue for improving cancer therapy strategies.

Citation

Fan Zhang, Zihua Gong. Regulation of DNA double-strand break repair pathway choice: a new focus on 53BP1. Journal of Zhejiang University. Science. B. 2021 Jan 15;22(1):38-46