KAP1 Deacetylation by SIRT1 Promotes Non-Homologous End-Joining Repair
Open Access
- 23 April 2015
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 10 (4), e0123935
- https://doi.org/10.1371/journal.pone.0123935
Abstract
Homologous recombination and non-homologous end joining are two major DNA double-strand-break repair pathways. While HR-mediated repair requires a homologous sequence as the guiding template to restore the damage site precisely, NHEJ-mediated repair ligates the DNA lesion directly and increases the risk of losing nucleotides. Therefore, how a cell regulates the balance between HR and NHEJ has become an important issue for maintaining genomic integrity over time. Here we report that SIRT1-dependent KAP1 deacetylation positively regulates NHEJ. We show that up-regulation of KAP1 attenuates HR efficiency while promoting NHEJ repair. Moreover, SIRT1-mediated KAP1 deacetylation further enhances the effect of NHEJ by stabilizing its interaction with 53BP1, which leads to increased 53BP1 focus formation in response to DNA damage. Taken together, our study suggests a SIRT1-KAP1 regulatory mechanism for HR-NHEJ repair pathway choice.This publication has 94 references indexed in Scilit:
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