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On-line Access: 2024-08-27

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 ORCID:

Zihua GONG

https://orcid.org/0000-0002-8008-0615

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Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.1 P.38-46

http://doi.org/10.1631/jzus.B2000306


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


Author(s):  Fan ZHANG, Zihua GONG

Affiliation(s):  Department of Cancer Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA

Corresponding email(s):   gongz@ccf.org

Key Words:  P53-binding protein 1 (53BP1), DNA double-strand break (DSB), Non-homologous end-joining (NHEJ), Homologous recombination (HR), Poly(ADP-ribose) polymerase inhibitor (PARPi)


Fan ZHANG, Zihua GONG. Regulation of DNA double-strand break repair pathway choice: a new focus on 53BP1[J]. Journal of Zhejiang University Science B, 2021, 22(1): 38-46.

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author="Fan ZHANG, Zihua GONG",
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year="2021",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2000306"
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%T Regulation of DNA double-strand break repair pathway choice: a new focus on 53BP1
%A Fan ZHANG
%A Zihua GONG
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T1 - Regulation of DNA double-strand break repair pathway choice: a new focus on 53BP1
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2000306


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.

DNA双链断裂修复途径选择的调控:53BP1蛋白最新研究关注

概要:DNA双链断裂(DSB)信号转导的关键作用是维持细胞的稳态和基因组的完整性。P53结合蛋白1(53BP1)在DSB修复信号选择中起到了关键的调节作用:53BP1能够促进DSB末端重新连接,从而促进非同源末端链接(NHEJ)介导的DSB修复途径。53BP1如何被招募到DNA损伤位点以及53BP1如何招募其DNA损伤修复效应子,从而促进NHEJ介导的DSB修复,并抑制同源重组(HR)信号传导?最新的研究对于这些问题有了进一步的阐述。这篇综述将着重于阐述53BP1蛋白是如何促进NHEJ介导的DSB修复途径以及其上下游通路蛋白调控,从而促进BRCA1缺陷型癌症细胞对多聚ADP-核糖聚合酶抑制剂(PARPi)的敏感性,最终为改善癌症治疗策略提供新的方向。

关键词:P53结合蛋白1(53BP1);DNA双链断裂(DSB);非同源末端链接(NHEJ);同源重组(HR);多聚ADP-核糖聚合酶抑制剂(PARPi)

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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