The fellowship of the RING: BRCA1, its partner BARD1 and their liaison in DNA repair and cancer

Pharmacol Ther. 2022 Apr;232:108009. doi: 10.1016/j.pharmthera.2021.108009. Epub 2021 Oct 4.

Abstract

The breast cancer type 1 susceptibility protein (BRCA1) and its partner - the BRCA1-associated RING domain protein 1 (BARD1) - are key players in a plethora of fundamental biological functions including, among others, DNA repair, replication fork protection, cell cycle progression, telomere maintenance, chromatin remodeling, apoptosis and tumor suppression. However, mutations in their encoding genes transform them into dangerous threats, and substantially increase the risk of developing cancer and other malignancies during the lifetime of the affected individuals. Understanding how BRCA1 and BARD1 perform their biological activities therefore not only provides a powerful mean to prevent such fatal occurrences but can also pave the way to the development of new targeted therapeutics. Thus, through this review work we aim at presenting the major efforts focused on the functional characterization and structural insights of BRCA1 and BARD1, per se and in combination with all their principal mediators and regulators, and on the multifaceted roles these proteins play in the maintenance of human genome integrity.

Keywords: BARD1; BRCA1; Cancer; DNA repair; Genome integrity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • BRCA1 Protein* / genetics
  • BRCA1 Protein* / metabolism
  • DNA Repair
  • Fellowships and Scholarships
  • Humans
  • Neoplasms* / genetics
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Tumor Suppressor Proteins
  • BARD1 protein, human
  • Ubiquitin-Protein Ligases