Regulation of DNA double-strand break repair pathway choice: a new focus on 53BP1 |
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| Authors: | Zhang Fan Gong Zihua |
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| Institution: | 1.Department of Cancer Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH, 44195, USA
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| Abstract: | 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. |
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| Keywords: | P53-binding protein 1 (53BP1) DNA double-strand break (DSB) Non-homologous end-joining (NHEJ) Homologous recombination (HR) Poly(ADP-ribose) polymerase inhibitor (PARPi) |
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