Title: The BRCA Tumor Suppressor Network in Chromosome Damage Repair by Homologous Recombination.
Authors: Zhao, Weixing; Wiese, Claudia; Kwon, Youngho; Hromas, Robert; Sung, Patrick
Published In Annu Rev Biochem, (2019 06 20)
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.
PubMed ID: 30917004
MeSH Terms: BRCA1 Protein/chemistry; BRCA1 Protein/genetics*; BRCA1 Protein/metabolism; BRCA2 Protein/chemistry; BRCA2 Protein/genetics*; BRCA2 Protein/metabolism; Binding Sites; Breast Neoplasms/genetics*; Breast Neoplasms/metabolism; Breast Neoplasms/pathology; DNA Breaks, Double-Stranded; DNA Replication; DNA/chemistry; DNA/genetics; DNA/metabolism; Female; Gene Regulatory Networks*; Genome, Human; Genomic Instability; Humans; Models, Molecular; Protein Binding; Protein Structure, Secondary; Rad51 Recombinase/chemistry; Rad51 Recombinase/genetics*; Rad51 Recombinase/metabolism; Recombinational DNA Repair*; Tumor Suppressor Proteins/chemistry; Tumor Suppressor Proteins/genetics*; Tumor Suppressor Proteins/metabolism; Ubiquitin-Protein Ligases/chemistry; Ubiquitin-Protein Ligases/genetics*; Ubiquitin-Protein Ligases/metabolism