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PLoS One. 2015 Apr 23;10(4):e0123935. doi: 10.1371/journal.pone.0123935. eCollection 2015.

KAP1 Deacetylation by SIRT1 Promotes Non-Homologous End-Joining Repair.

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Department of Biochemistry and Molecular Biology, Mayo Graduate School, Rochester, Minnesota, United States of America.
Research Center for Translational Medicine, Tongji University School of Medicine, Shanghai, China; Key Laboratory of Arrhythmias of the Ministry of Education of China East Hospital, Tongji University School of Medicine, Shanghai, China.
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, Minnesota, United States of America.
Department of Molecular Pharmacology and Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope, Duarte, California, United States of America.


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.

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