Article ; Online: mRNA Processing Factor CstF-50 and Ubiquitin Escort Factor p97 Are BRCA1/BARD1 Cofactors Involved in Chromatin Remodeling during the DNA Damage Response.
Molecular and cellular biology
2018 Volume 38, Issue 4
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) ...
| 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. |
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| MeSH term(s) | Adenosine Triphosphatases/genetics ; Adenosine Triphosphatases/metabolism ; BRCA1 Protein/genetics ; BRCA1 Protein/metabolism ; Chromatin Assembly and Disassembly ; Cleavage Stimulation Factor/genetics ; Cleavage Stimulation Factor/metabolism ; DNA Damage ; DNA Repair ; DNA-Binding Proteins/metabolism ; Histones/genetics ; Histones/metabolism ; Humans ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; RNA Polymerase II/genetics ; RNA Polymerase II/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination ; mRNA Cleavage and Polyadenylation Factors/metabolism |
| Chemical Substances | BRCA1 Protein ; BRCA1 protein, human ; Cleavage Stimulation Factor ; DNA-Binding Proteins ; Histones ; Nuclear Proteins ; RNA, Messenger ; Tumor Suppressor Proteins ; Ubiquitin ; mRNA Cleavage and Polyadenylation Factors ; BARD1 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; RNA Polymerase II (EC 2.7.7.-) ; Adenosine Triphosphatases (EC 3.6.1.-) ; p97 ATPase (EC 3.6.1.-) |
| Language | English |
| Publishing date | 2018-01-29 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 779397-2 |
| ISSN | 1098-5549 ; 0270-7306 |
| ISSN (online) | 1098-5549 |
| ISSN | 0270-7306 |
| DOI | 10.1128/MCB.00364-17 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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