BRCA1/BARD1 is a nucleosome reader and writer

Trends Biochem Sci. 2022 Jul;47(7):582-595. doi: 10.1016/j.tibs.2022.03.001. Epub 2022 Mar 26.


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.

Keywords: DNA damage repair; chromatin regulation; homologous recombination; transcriptional regulation; ubiquitin ligase.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • Nucleosomes*
  • Tumor Suppressor Proteins* / genetics
  • Tumor Suppressor Proteins* / metabolism
  • Ubiquitin-Protein Ligases / metabolism


  • BRCA1 Protein
  • Nucleosomes
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases