The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA.
Individuals with BRCA2 mutations are predisposed to breast cancers owing to genome instability. To determine the functions of BRCA2, the human protein was purified. It was found to bind selectively to single-stranded DNA (ssDNA), and to ssDNA in tailed duplexes and replication fork structures. Monomeric and dimeric forms of BRCA2 were observed by EM. BRCA2 directed the binding of RAD51 recombinase to ssDNA, reduced the binding of RAD51 to duplex DNA and stimulated RAD51-mediated DNA strand exchange. These observations provide a molecular basis for the role of BRCA2 in the maintenance of genome stability.
Thorslund
Tina
T
London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Hertfordshire, UK.
McIlwraith
Michael J
MJ
Compton
Sarah A
SA
Lekomtsev
Sergey
S
Petronczki
Mark
M
Griffith
Jack D
JD
West
Stephen C
SC
D020816:Amino Acid Motifs; D051017:Apoptosis Regulatory Proteins; D024682:BRCA2 Protein / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D001943:Breast Neoplasms / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008854:Microscopy, Electron; D009363:Neoplasm Proteins / Q000737:chemistry / Q000502:physiology; D011485:Protein Binding; D025941:Protein Interaction Mapping; D051135:Rad51 Recombinase / Q000737:chemistry / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004277:DNA, Single-Stranded; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D004247:DNA; C495153:RAD51 protein, human; D051135:Rad51 Recombinase