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KAP1 Deacetylation by SIRT1 Promotes Non-Homologous End-Joining Repair
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408008/ https://www.ncbi.nlm.nih.gov/pubmed/25905708 http://dx.doi.org/10.1371/journal.pone.0123935 |
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author | Lin, Yi-Hui Yuan, Jian Pei, Huadong Liu, Tongzheng Ann, David K. Lou, Zhenkun |
author_facet | Lin, Yi-Hui Yuan, Jian Pei, Huadong Liu, Tongzheng Ann, David K. Lou, Zhenkun |
author_sort | Lin, Yi-Hui |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4408008 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44080082015-05-04 KAP1 Deacetylation by SIRT1 Promotes Non-Homologous End-Joining Repair Lin, Yi-Hui Yuan, Jian Pei, Huadong Liu, Tongzheng Ann, David K. Lou, Zhenkun PLoS One Research Article 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. Public Library of Science 2015-04-23 /pmc/articles/PMC4408008/ /pubmed/25905708 http://dx.doi.org/10.1371/journal.pone.0123935 Text en © 2015 Lin et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lin, Yi-Hui Yuan, Jian Pei, Huadong Liu, Tongzheng Ann, David K. Lou, Zhenkun KAP1 Deacetylation by SIRT1 Promotes Non-Homologous End-Joining Repair |
title | KAP1 Deacetylation by SIRT1 Promotes Non-Homologous End-Joining Repair |
title_full | KAP1 Deacetylation by SIRT1 Promotes Non-Homologous End-Joining Repair |
title_fullStr | KAP1 Deacetylation by SIRT1 Promotes Non-Homologous End-Joining Repair |
title_full_unstemmed | KAP1 Deacetylation by SIRT1 Promotes Non-Homologous End-Joining Repair |
title_short | KAP1 Deacetylation by SIRT1 Promotes Non-Homologous End-Joining Repair |
title_sort | kap1 deacetylation by sirt1 promotes non-homologous end-joining repair |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408008/ https://www.ncbi.nlm.nih.gov/pubmed/25905708 http://dx.doi.org/10.1371/journal.pone.0123935 |
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