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USP19 deubiquitinates HDAC1/2 to regulate DNA damage repair and control chromosomal stability
Excessive accumulation of DNA damage will generate chromosome stress, leading to various chromosome abnormalities such as chromatin bridge and result in genomic instability. Orchestra procession and regulation of DNA damage repair are vital for keeping genome stability. Despite of the key role of HD...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356792/ https://www.ncbi.nlm.nih.gov/pubmed/27517492 http://dx.doi.org/10.18632/oncotarget.11116 |
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author | Wu, Min Tu, Hai-qing Chang, Yan Tan, Bo Wang, Guang Zhou, Jie Wang, Li Mu, Rui Zhang, Wei-na |
author_facet | Wu, Min Tu, Hai-qing Chang, Yan Tan, Bo Wang, Guang Zhou, Jie Wang, Li Mu, Rui Zhang, Wei-na |
author_sort | Wu, Min |
collection | PubMed |
description | Excessive accumulation of DNA damage will generate chromosome stress, leading to various chromosome abnormalities such as chromatin bridge and result in genomic instability. Orchestra procession and regulation of DNA damage repair are vital for keeping genome stability. Despite of the key role of HDAC1/2 in double strand break (DSB) repair, the regulation for their mode of action is less well understood. In this study, we found that deubiquitination enzymes USP19 physically interacts with HDAC1/2 and specifically regulate their K63-linked ubiquitination, which might be crucial for regulation of HDAC1/2 activity in DNA damage repair. Notably, we found that USP19 trans-locate into nucleus upon IR irradiation and is indispensable for normally DNA damage response. In addition, we showed that USP19 play critical role in preventing anaphase bridge formation through regulating DNA damage repair process. Furthermore, the expression level of USP19 is commonly lower or deleted in several types of tumor. These results indicated that USP19 is a key factor in modulating DNA damage repair by targeting HDAC1/2 K63-linked ubiquitination, cells with deletion or decreased expression of USP19 might cause genome instability and even contribute to tumorigenesis. |
format | Online Article Text |
id | pubmed-5356792 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53567922017-04-20 USP19 deubiquitinates HDAC1/2 to regulate DNA damage repair and control chromosomal stability Wu, Min Tu, Hai-qing Chang, Yan Tan, Bo Wang, Guang Zhou, Jie Wang, Li Mu, Rui Zhang, Wei-na Oncotarget Research Paper Excessive accumulation of DNA damage will generate chromosome stress, leading to various chromosome abnormalities such as chromatin bridge and result in genomic instability. Orchestra procession and regulation of DNA damage repair are vital for keeping genome stability. Despite of the key role of HDAC1/2 in double strand break (DSB) repair, the regulation for their mode of action is less well understood. In this study, we found that deubiquitination enzymes USP19 physically interacts with HDAC1/2 and specifically regulate their K63-linked ubiquitination, which might be crucial for regulation of HDAC1/2 activity in DNA damage repair. Notably, we found that USP19 trans-locate into nucleus upon IR irradiation and is indispensable for normally DNA damage response. In addition, we showed that USP19 play critical role in preventing anaphase bridge formation through regulating DNA damage repair process. Furthermore, the expression level of USP19 is commonly lower or deleted in several types of tumor. These results indicated that USP19 is a key factor in modulating DNA damage repair by targeting HDAC1/2 K63-linked ubiquitination, cells with deletion or decreased expression of USP19 might cause genome instability and even contribute to tumorigenesis. Impact Journals LLC 2016-08-08 /pmc/articles/PMC5356792/ /pubmed/27517492 http://dx.doi.org/10.18632/oncotarget.11116 Text en Copyright: © 2017 Wu et al. http://creativecommons.org/licenses/by/3.0/ 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 credited. |
spellingShingle | Research Paper Wu, Min Tu, Hai-qing Chang, Yan Tan, Bo Wang, Guang Zhou, Jie Wang, Li Mu, Rui Zhang, Wei-na USP19 deubiquitinates HDAC1/2 to regulate DNA damage repair and control chromosomal stability |
title | USP19 deubiquitinates HDAC1/2 to regulate DNA damage repair and control chromosomal stability |
title_full | USP19 deubiquitinates HDAC1/2 to regulate DNA damage repair and control chromosomal stability |
title_fullStr | USP19 deubiquitinates HDAC1/2 to regulate DNA damage repair and control chromosomal stability |
title_full_unstemmed | USP19 deubiquitinates HDAC1/2 to regulate DNA damage repair and control chromosomal stability |
title_short | USP19 deubiquitinates HDAC1/2 to regulate DNA damage repair and control chromosomal stability |
title_sort | usp19 deubiquitinates hdac1/2 to regulate dna damage repair and control chromosomal stability |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356792/ https://www.ncbi.nlm.nih.gov/pubmed/27517492 http://dx.doi.org/10.18632/oncotarget.11116 |
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