BRCA2 coordinates the activities of cell-cycle kinases to promote genome stability.

Abstract	Numerous human genome instability syndromes, including cancer, are closely associated with events arising from malfunction of the essential recombinase Rad51. However, little is known about how Rad51 is dynamically regulated in human cells. Here, we show that the breast cancer susceptibility protein BRCA2, a key Rad51 binding partner, coordinates the activity of the central cell-cycle drivers CDKs and Plk1 to promote Rad51-mediated genome stability control. The soluble nuclear fraction of BRCA2 binds Plk1 directly in a cell-cycle- and CDK-dependent manner and acts as a molecular platform to facilitate Plk1-mediated Rad51 phosphorylation. This phosphorylation is important for enhancing the association of Rad51 with stressed replication forks, which in turn protects the genomic integrity of proliferating human cells. This study reveals an elaborate but highly organized molecular interplay between Rad51 regulators and has significant implications for understanding tumorigenesis and therapeutic resistance in patients with BRCA2 deficiency.
Authors	Keiko Yata, Jean-Yves Bleuyard, Ryuichiro Nakato, Christine Ralf, Yuki Katou, Rebekka A Schwab, Wojciech Niedzwiedz, Katsuhiko Shirahige, Fumiko Esashi
Journal	Cell reports (Cell Rep) Vol. 7 Issue 5 Pg. 1547-1559 (Jun 12 2014) ISSN: 2211-1247 [Electronic] United States
PMID	24835992 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References	BRCA2 Protein BRCA2 protein, human Cell Cycle Proteins Proto-Oncogene Proteins Protein Serine-Threonine Kinases polo-like kinase 1 CDK2 protein, human Cyclin-Dependent Kinase 2 Exonucleases Rad1 protein, human
Topics	BRCA2 Protein (genetics, metabolism) Cell Cycle Proteins (metabolism) Cyclin-Dependent Kinase 2 (metabolism) DNA Replication Exonucleases (metabolism) Genomic Instability HEK293 Cells HeLa Cells Humans Protein Binding Protein Serine-Threonine Kinases (metabolism) Proto-Oncogene Proteins (metabolism)

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