Rapid Recruitment of P53 to DNA Damage Sites Directs DNA Repair Choice and Integrity

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2022 Mar 2

PMID 35235448

Authors

Yu-Hsiu Wang

Teresa L F Ho

Anushya Hariharan

Hui Chin Goh

Yao Liang Wong

Nicole S Verkaik

May Yin Lee

Wai Leong Tam

Dik C van Gent

Ashok R Venkitaraman

Michael P Sheetz

David P Lane

Affiliations

Soon will be listed here.

Abstract

SignificanceOur work focuses on the critical longstanding question of the nontranscriptional role of p53 in tumor suppression. We demonstrate here that poly(ADP-ribose) polymerase (PARP)-dependent modification of p53 enables rapid recruitment of p53 to damage sites, where it in turn directs early repair pathway selection. Specifically, p53-mediated recruitment of 53BP1 at early time points promotes nonhomologous end joining over the more error-prone microhomology end-joining. Similarly, p53 directs nucleotide excision repair by mediating DDB1 recruitment. This property of p53 also correlates with tumor suppression in vivo. Our study provides mechanistic insight into how certain transcriptionally deficient p53 mutants may retain tumor-suppressive functions through regulating the DNA damage response.

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