mRNA processing factor CstF-50 and ubiquitin escort factor p97 are BRCA1/BARD1 cofactors involved in chromatin remodeling during the DNA damage response

Danae Fonseca, Jorge Baquero, Michael R. Murphy, Gamage Aruggoda, Sophia Varriano, Carmen Sapienza, Oksana Mashadova, Shadaqur Rahman, Frida E. Kleiman

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Article numbere00364-17
JournalMolecular and Cellular Biology
Volume38
Issue number4
DOIs
StatePublished - 1 Feb 2018

Keywords

  • BRCA1/BARD1
  • Chromatin remodeling
  • CstF-50
  • DNA damage response
  • Histones
  • P97
  • RNA polymerase II

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