mRNA Processing Factor CstF-50 and Ubiquitin Escort Factor p97 Are BRCA1/BARD1 Cofactors Involved in Chromatin Remodeling during the DNA Damage Response

The cellular response to DNA damage is an intricate mechanism that involves the interplay among several pathways. In this study, we provide evidence of the roles of the polyadenylation factor cleavage stimulation factor 50 (CstF-50) and the ubiquitin (Ub) escort factor p97 as cofactors of BRCA1/BARD...

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Published inMolecular and cellular biology Vol. 38; no. 4
Main Authors Fonseca, Danae, Baquero, Jorge, Murphy, Michael R., Aruggoda, Gamage, Varriano, Sophia, Sapienza, Carmen, Mashadova, Oksana, Rahman, Shadaqur, Kleiman, Frida E.
Format Journal Article
LanguageEnglish
Published United States Taylor & Francis 01.02.2018
American Society for Microbiology
Subjects
BRCA1/BARD1
chromatin remodeling
CstF-50
DNA damage response
histones
RNA polymerase II
BRCA1/BARD1
histones
DNA damage response
CstF-50
chromatin remodeling
RNA polymerase II
p97
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Abstract The cellular response to DNA damage is an intricate mechanism that involves the interplay among several pathways. In this study, we provide evidence of the roles of the polyadenylation factor cleavage stimulation factor 50 (CstF-50) and the ubiquitin (Ub) escort factor p97 as cofactors of BRCA1/BARD1 E3 Ub ligase, facilitating chromatin remodeling during the DNA damage response (DDR). CstF-50 and p97 formed complexes with BRCA1/BARD1, Ub, and some BRCA1/BARD1 substrates, such as RNA polymerase (RNAP) II and histones. Furthermore, CstF-50 and p97 had an additive effect on the activation of the ubiquitination of these BRCA1/BARD1 substrates during DDR. Importantly, as a result of these functional interactions, BRCA1/BARD1/CstF-50/p97 had a specific effect on the chromatin structure of genes that were differentially expressed. This study provides new insights into the roles of RNA processing, BRCA1/BARD1, the Ub pathway, and chromatin structure during DDR.
AbstractList The cellular response to DNA damage is an intricate mechanism that involves the interplay among several pathways. In this study, we provide evidence of the roles of the polyadenylation factor cleavage stimulation factor 50 (CstF-50) and the ubiquitin (Ub) escort factor p97 as cofactors of BRCA1/BARD1 E3 Ub ligase, facilitating chromatin remodeling during the DNA damage response (DDR). CstF-50 and p97 formed complexes with BRCA1/BARD1, Ub, and some BRCA1/BARD1 substrates, such as RNA polymerase (RNAP) II and histones. Furthermore, CstF-50 and p97 had an additive effect on the activation of the ubiquitination of these BRCA1/BARD1 substrates during DDR. Importantly, as a result of these functional interactions, BRCA1/BARD1/CstF-50/p97 had a specific effect on the chromatin structure of genes that were differentially expressed. This study provides new insights into the roles of RNA processing, BRCA1/BARD1, the Ub pathway, and chromatin structure during DDR.
Author Baquero, Jorge
Sapienza, Carmen
Murphy, Michael R.
Aruggoda, Gamage
Varriano, Sophia
Mashadova, Oksana
Rahman, Shadaqur
Kleiman, Frida E.
Fonseca, Danae
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Issue 4
Keywords BRCA1/BARD1
histones
DNA damage response
CstF-50
chromatin remodeling
RNA polymerase II
p97
Language English
License open-access: https://creativecommons.org/licenses/by/4.0/: This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Copyright © 2018 Fonseca et al.
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Present address: Danae Fonseca, Microbiology Department, Icahn School of Medicine, Mount Sinai, New York, New York, USA; Oksana Mashadova, Meyer Cancer Center, Weill Cornell Medicine, New York, New York, USA.
Citation Fonseca D, Baquero J, Murphy MR, Aruggoda G, Varriano S, Sapienza C, Mashadova O, Rahman S, Kleiman FE. 2018. mRNA processing factor CstF-50 and ubiquitin escort factor p97 are BRCA1/BARD1 cofactors involved in chromatin remodeling during the DNA damage response. Mol Cell Biol 38:e00364-17. https://doi.org/10.1128/MCB.00364-17.
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Snippet The cellular response to DNA damage is an intricate mechanism that involves the interplay among several pathways. In this study, we provide evidence of the...
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SubjectTerms BRCA1/BARD1
chromatin remodeling
CstF-50
DNA damage response
histones
RNA polymerase II
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Title mRNA Processing Factor CstF-50 and Ubiquitin Escort Factor p97 Are BRCA1/BARD1 Cofactors Involved in Chromatin Remodeling during the DNA Damage Response
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