Interaction with the BRCA2 C terminus protects RAD51-DNA filaments from disassembly by BRC repeats.
BRCA2 has an essential function in DNA repair by homologous recombination, interacting with RAD51 via short motifs in the middle and at the C terminus of BRCA2. Here, we report that a conserved 36-residue sequence of human BRCA2 encoded by exon 27 (BRCA2Exon27) interacts with RAD51 through the specific recognition of oligomerized RAD51 ATPase domains. BRCA2Exon27 binding stabilizes the RAD51 nucleoprotein filament against disassembly by BRC repeat 4. The protection is specific for RAD51 filaments formed on single-stranded DNA and is lost when BRCA2Exon27 is phosphorylated on Ser3291. We propose that productive recombination results from the functional balance between the different RAD51-binding modes [corrected] of the BRC repeat and exon 27 regions of BRCA2. Our results further suggest a mechanism in which CDK phosphorylation of BRCA2Exon27 at the G2-M transition alters the balance in favor of RAD51 filament disassembly, thus terminating recombination.
Davies
Owen Richard
OR
University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge CB2 1GA, UK.
Pellegrini
Luca
L
D000595:Amino Acid Sequence; 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; D004587:Electrophoresis, Agar Gel; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic / Q000235:genetics / Q000502:physiology*; D020079:Terminal Repeat Sequences / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D009698:Nucleoproteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase