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mRNA Processing Factor CstF-50 and Ubiquitin Escort Factor p97 Are BRCA1/BARD1 Cofactors Involved in Chromatin

Danae Fonseca1, Jorge Baquero1, Michael R Murphy1

  • 1Chemistry Department, Hunter College and Biochemistry Program, Graduate Center, City University of New York, New York, New York, USA.

Molecular and Cellular Biology
|November 29, 2017
PubMed

Insights

The study reveals how cleavage stimulation factor 50 (CstF-50) and p97 protein aid BRCA1/BARD1 in DNA damage response by remodeling chromatin. This interaction influences gene expression during DNA repair.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • The DNA damage response (DDR) involves complex cellular pathways to maintain genomic integrity.
  • BRCA1/BARD1 acts as a crucial E3 ubiquitin ligase in DNA repair and other cellular processes.
  • Chromatin remodeling is essential for regulating gene accessibility during DDR.

Purpose of the Study:

  • To investigate the roles of CstF-50 and p97 as cofactors in the BRCA1/BARD1 E3 ligase complex during DDR.
  • To elucidate the impact of these interactions on chromatin structure and gene expression in response to DNA damage.

Main Methods:

  • Co-immunoprecipitation assays to detect protein complex formation.
  • Ubiquitination assays to measure substrate modification.
  • Chromatin analysis to assess structural changes and gene expression patterns.

Main Results:

  • CstF-50 and p97 form complexes with BRCA1/BARD1, ubiquitin, and key substrates like RNA polymerase II and histones.
  • CstF-50 and p97 exhibit an additive effect on the ubiquitination of BRCA1/BARD1 substrates during DDR.
  • The BRCA1/BARD1/CstF-50/p97 complex specifically alters chromatin structure in differentially expressed genes.

Conclusions:

  • CstF-50 and p97 function as cofactors for BRCA1/BARD1 E3 ligase, facilitating chromatin remodeling in DDR.
  • These findings highlight the interplay between RNA processing factors, ubiquitin pathways, and chromatin dynamics in DNA damage response.
  • The study offers new insights into the molecular mechanisms governing gene expression regulation following DNA damage.
Keywords:
BRCA1/BARD1CstF-50DNA damage responseRNA polymerase IIchromatin remodelinghistonesp97

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