BRCA1/BARD1 is a nucleosome reader and writer

Samuel R. Witus, Weixing Zhao, Peter S. Brzovic, Rachel E. Klevit

Research output: Contribution to journalReview articlepeer-review

Abstract

Mutations in BRCA1 and BARD1 predispose carriers to breast and ovarian cancers. The BRCA1 and BARD1 proteins form a heterodimeric complex (BRCA1/BARD1) that regulates many biological processes, including transcription and DNA double-stranded break repair. These functions are mediated by the only known enzymatic activity of BRCA1/BARD1 in its capacity as an E3 ubiquitin ligase and its role as a central hub for many large protein complexes. But the mechanisms by which BRCA1/BARD1 interfaces with chromatin, where it exerts its major functions, have remained unknown. Here, we review recent advancements in structural and cellular biology that have provided critical insights into how BRCA1/BARD1 serves as both a nucleosome reader and writer to facilitate transcriptional regulation and DNA repair by homologous recombination.

Original languageEnglish (US)
Pages (from-to)582-595
Number of pages14
JournalTrends in Biochemical Sciences
Volume47
Issue number7
DOIs
StatePublished - Jul 2022

Keywords

  • DNA damage repair
  • chromatin regulation
  • homologous recombination
  • transcriptional regulation
  • ubiquitin ligase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Fingerprint

Dive into the research topics of 'BRCA1/BARD1 is a nucleosome reader and writer'. Together they form a unique fingerprint.

Cite this