The BRCA tumor suppressor network in chromosome damage repair by homologous recombination

Research output: Contribution to journalReview article

11 Scopus citations

Abstract

Mutations in the BRCA1 and BRCA2 genes predispose afflicted individuals to breast, ovarian, and other cancers. The BRCA-encoded products form complexes with other tumor suppressor proteins and with the recombinase enzyme RAD51 to mediate chromosome damage repair by homologous recombination and also to protect stressed DNA replication forks against spurious nucleolytic attrition. Understanding how the BRCA tumor suppressor network executes its biological functions would provide the foundation for developing targeted cancer therapeutics, but progress in this area has been greatly hampered by the challenge of obtaining purified BRCA complexes for mechanistic studies. In this article, we review how recent effort begins to overcome this technical challenge, leading to functional and structural insights into the biochemical attributes of these complexes and the multifaceted roles that they fulfill in genome maintenance. We also highlight the major mechanistic questions that remain.

Original languageEnglish (US)
Pages (from-to)221-245
Number of pages25
JournalAnnual Review of Biochemistry
Volume88
DOIs
StatePublished - Jun 20 2019

Keywords

  • BARD1
  • BRCA1
  • BRCA2
  • DNA damage repair
  • genome maintenance
  • homologous recombination
  • replication fork protection
  • replication fork repair
  • tumor suppression

ASJC Scopus subject areas

  • Biochemistry

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