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The BRCA1 Ubiquitin ligase function sets a new trend for remodelling in DNA repair

The protein product of the breast and ovarian cancer gene, BRCA1, is part of an obligate heterodimer with BARD1. Together these RING bearing proteins act as an E3 ubiquitin ligase. Several functions have been attributed to BRCA1 that contribute to genome integrity but which of these, if any, require...

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Autores principales: Densham, Ruth M., Morris, Joanna R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403137/
https://www.ncbi.nlm.nih.gov/pubmed/28032817
http://dx.doi.org/10.1080/19491034.2016.1267092
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author Densham, Ruth M.
Morris, Joanna R.
author_facet Densham, Ruth M.
Morris, Joanna R.
author_sort Densham, Ruth M.
collection PubMed
description The protein product of the breast and ovarian cancer gene, BRCA1, is part of an obligate heterodimer with BARD1. Together these RING bearing proteins act as an E3 ubiquitin ligase. Several functions have been attributed to BRCA1 that contribute to genome integrity but which of these, if any, require this enzymatic function was unclear. Here we review recent studies clarifying the role of BRCA1 E3 ubiquitin ligase in DNA repair. Perhaps the most surprising finding is the narrow range of BRCA1 functions this activity relates to. Remarkably ligase activity promotes chromatin remodelling and 53BP1 positioning through the remodeller SMARCAD1, but the activity is dispensable for the cellular survival in response to cisplatin or replication stressing agents. Implications for therapy response and tumor susceptibility are discussed.
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spelling pubmed-54031372017-05-03 The BRCA1 Ubiquitin ligase function sets a new trend for remodelling in DNA repair Densham, Ruth M. Morris, Joanna R. Nucleus Extra View The protein product of the breast and ovarian cancer gene, BRCA1, is part of an obligate heterodimer with BARD1. Together these RING bearing proteins act as an E3 ubiquitin ligase. Several functions have been attributed to BRCA1 that contribute to genome integrity but which of these, if any, require this enzymatic function was unclear. Here we review recent studies clarifying the role of BRCA1 E3 ubiquitin ligase in DNA repair. Perhaps the most surprising finding is the narrow range of BRCA1 functions this activity relates to. Remarkably ligase activity promotes chromatin remodelling and 53BP1 positioning through the remodeller SMARCAD1, but the activity is dispensable for the cellular survival in response to cisplatin or replication stressing agents. Implications for therapy response and tumor susceptibility are discussed. Taylor & Francis 2016-12-29 /pmc/articles/PMC5403137/ /pubmed/28032817 http://dx.doi.org/10.1080/19491034.2016.1267092 Text en © 2017 The Author(s). Published with license by Taylor & Francis http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Extra View
Densham, Ruth M.
Morris, Joanna R.
The BRCA1 Ubiquitin ligase function sets a new trend for remodelling in DNA repair
title The BRCA1 Ubiquitin ligase function sets a new trend for remodelling in DNA repair
title_full The BRCA1 Ubiquitin ligase function sets a new trend for remodelling in DNA repair
title_fullStr The BRCA1 Ubiquitin ligase function sets a new trend for remodelling in DNA repair
title_full_unstemmed The BRCA1 Ubiquitin ligase function sets a new trend for remodelling in DNA repair
title_short The BRCA1 Ubiquitin ligase function sets a new trend for remodelling in DNA repair
title_sort brca1 ubiquitin ligase function sets a new trend for remodelling in dna repair
topic Extra View
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403137/
https://www.ncbi.nlm.nih.gov/pubmed/28032817
http://dx.doi.org/10.1080/19491034.2016.1267092
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