Article abstract
Nature Structural & Molecular Biology 14, 468 - 474 (2007)
Published online: 21 May 2007 | doi:10.1038/nsmb1245
Stabilization of RAD51 nucleoprotein filaments by the C-terminal region of BRCA2
Fumiko Esashi1, Vitold E Galkin2, Xiong Yu2, Edward H Egelman2 & Stephen C West1
Abstract
The human breast cancer susceptibility gene BRCA2 is required for the regulation of RAD51-mediated homologous recombinational repair. BRCA2 interacts with RAD51 monomers, as well as nucleoprotein filaments, primarily though the conserved BRC motifs. The unrelated C-terminal region of BRCA2 also interacts with RAD51. Here we show that the BRCA2 C terminus interacts directly with RAD51 filaments, but not monomers, by binding an interface created by two adjacent RAD51 protomers. These interactions stabilize filaments so that they cannot be dissociated by association with BRC repeats. Interaction of the BRCA2 C terminus with the RAD51 filament causes a large movement of the flexible RAD51 N-terminal domain that is important in regulating filament dynamics. We suggest that interactions of the BRCA2 C-terminal region with RAD51 may facilitate efficient nucleation of RAD51 multimers on DNA and thereby stimulate recombination-mediated repair.
- Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.
- Department of Biochemistry and Molecular Genetics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908-0733, USA.
Correspondence to: Stephen C West1 e-mail: stephen.west@cancer.org.uk
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