Stabilization of RAD51 nucleoprotein filaments by the C-terminal region of BRCA2.
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.
Esashi
Fumiko
F
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.
Galkin
Vitold E
VE
Yu
Xiong
X
Egelman
Edward H
EH
West
Stephen C
SC
D051017:Apoptosis Regulatory Proteins; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism*; D002850:Chromatography, Gel; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics* / Q000502:physiology; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D008854:Microscopy, Electron; D008954:Models, Biological; D008958:Models, Molecular; D009698:Nucleoproteins / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D009698:Nucleoproteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase