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

Authors
  • Fonseca, Danae1
  • Baquero, Jorge1
  • Murphy, Michael R1
  • Aruggoda, Gamage1
  • Varriano, Sophia1
  • Sapienza, Carmen2
  • Mashadova, Oksana1
  • Rahman, Shadaqur1
  • Kleiman, Frida E3
  • 1 Chemistry Department, Hunter College and Biochemistry Program, Graduate Center, City University of New York, New York, New York, USA.
  • 2 Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
  • 3 Chemistry Department, Hunter College and Biochemistry Program, Graduate Center, City University of New York, New York, New York, USA [email protected]
Type
Published Article
Journal
Molecular and Cellular Biology
Publisher
American Society for Microbiology
Publication Date
Feb 15, 2018
Volume
38
Issue
4
Identifiers
DOI: 10.1128/MCB.00364-17
PMID: 29180510
Source
Medline
Keywords
License
Unknown

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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