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

DNA双链断裂修复途径选择的调控:53BP1蛋白最新研究关注

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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.

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。

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  • 08 April 2021

    The typesetting format of the online version of the first issue (2021 22(01)) of Journal of Zhejiang University-SCIENCE B is different from that of the printed version (but all the text, figure and table contents in the article are correct). This is due to the new typesetting company adopted this year.

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Fan ZHANG wrote and edited the manuscript and drew the figures. Zihua GONG contributed to the revision of the manuscript and the figures. Both authors have read and approved the final manuscript and, therefore, take responsibility for the integrity and security of the manuscript.

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Correspondence to Zihua Gong.

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Fan ZHANG and Zihua GONG declare that they have no conflict of interest.

This paper does not contain any studies with human or animal subjects performed by either of the authors.

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Zhang, F., Gong, Z. Regulation of DNA double-strand break repair pathway choice: a new focus on 53BP1. J. Zhejiang Univ. Sci. B 22, 38–46 (2021). https://doi.org/10.1631/jzus.B2000306

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  • DOI: https://doi.org/10.1631/jzus.B2000306

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