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The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair
Histone/protein deacetylases play multiple roles in regulating gene expression and protein activation and stability. Their deregulation during cancer initiation and progression cause resistance to therapy. Here, we review the role of histone deacetylases (HDACs) and the NAD(+) dependent sirtuins (SI...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137451/ https://www.ncbi.nlm.nih.gov/pubmed/27738139 http://dx.doi.org/10.1093/nar/gkw922 |
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author | Roos, Wynand Paul Krumm, Andrea |
author_facet | Roos, Wynand Paul Krumm, Andrea |
author_sort | Roos, Wynand Paul |
collection | PubMed |
description | Histone/protein deacetylases play multiple roles in regulating gene expression and protein activation and stability. Their deregulation during cancer initiation and progression cause resistance to therapy. Here, we review the role of histone deacetylases (HDACs) and the NAD(+) dependent sirtuins (SIRTs) in the DNA damage response (DDR). These lysine deacetylases contribute to DNA repair by base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), non-homologous end joining (NHEJ), homologous recombination (HR) and interstrand crosslink (ICL) repair. Furthermore, we discuss possible mechanisms whereby these histone/protein deacetylases facilitate the switch between DNA double-strand break (DSB) repair pathways, how SIRTs play a central role in the crosstalk between DNA repair and cell death pathways due to their dependence on NAD(+), and the influence of small molecule HDAC inhibitors (HDACi) on cancer cell resistance to genotoxin based therapies. Throughout the review, we endeavor to identify the specific HDAC targeted by HDACi leading to therapy sensitization. |
format | Online Article Text |
id | pubmed-5137451 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-51374512016-12-06 The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair Roos, Wynand Paul Krumm, Andrea Nucleic Acids Res Survey and Summary Histone/protein deacetylases play multiple roles in regulating gene expression and protein activation and stability. Their deregulation during cancer initiation and progression cause resistance to therapy. Here, we review the role of histone deacetylases (HDACs) and the NAD(+) dependent sirtuins (SIRTs) in the DNA damage response (DDR). These lysine deacetylases contribute to DNA repair by base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), non-homologous end joining (NHEJ), homologous recombination (HR) and interstrand crosslink (ICL) repair. Furthermore, we discuss possible mechanisms whereby these histone/protein deacetylases facilitate the switch between DNA double-strand break (DSB) repair pathways, how SIRTs play a central role in the crosstalk between DNA repair and cell death pathways due to their dependence on NAD(+), and the influence of small molecule HDAC inhibitors (HDACi) on cancer cell resistance to genotoxin based therapies. Throughout the review, we endeavor to identify the specific HDAC targeted by HDACi leading to therapy sensitization. Oxford University Press 2016-12-01 2016-10-13 /pmc/articles/PMC5137451/ /pubmed/27738139 http://dx.doi.org/10.1093/nar/gkw922 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Survey and Summary Roos, Wynand Paul Krumm, Andrea The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair |
title | The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair |
title_full | The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair |
title_fullStr | The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair |
title_full_unstemmed | The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair |
title_short | The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair |
title_sort | multifaceted influence of histone deacetylases on dna damage signalling and dna repair |
topic | Survey and Summary |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137451/ https://www.ncbi.nlm.nih.gov/pubmed/27738139 http://dx.doi.org/10.1093/nar/gkw922 |
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