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Annu Rev Biochem. 2019 Mar 27. doi: 10.1146/annurev-biochem-013118-111058. [Epub ahead of print]

The BRCA Tumor Suppressor Network in Chromosome Damage Repair by Homologous Recombination.

Zhao W1,2,3, Wiese C4,3, Kwon Y1,2, Hromas R5, Sung P1,2.

Author information

1
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
2
Department of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, Texas 78229, USA; email: zhaow2@uthscsa.edu , sungp@uthscsa.edu.
3
These authors contributed equally to this article.
4
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.
5
Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas 78229, USA.

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. Expected final online publication date for the Annual Review of Biochemistry Volume 88 is June 20, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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