Biology Reference
In-Depth Information
A
BRC repeats
DBD
123456 78
PhePP
PALB2
RAD51
DMC1
DSS1
RAD51
B
Double-strand break
5
¢
-3
¢
Resection and RPA binding
BRCA2 nucleates RAD51 on ssDNA displacing RPA
while preventing assembly on dsDNA
RAD51 nucleoprotein filament growth
BRCA2
RAD51
RPA
F
IG
. 5. BRCA2 and its proposed role in homologous recombination (HR). (A) Schematic
representation of the functional and structural domains of human BRCA2. (B) Upon formation of a
double-strand break (DSB), the 5
0
strand is resected to leave a 3
0
ssDNA. Replication protein
A (RPA) binds and prevents secondary structure formation. BRCA2 binds at the dsDNA-ssDNA
junction and initiates RAD51 nucleation on RPA-coated ssDNA while limiting nucleation on
dsDNA. Continued RAD51 nucleoprotein filament growth results in a functional nucleoprotein
filament that performs a homology search and strand exchange.
preferential filament formation of RAD51.
195
The collective action of these two
BRC groups can facilitate RAD51 nucleation and nascent filament formation
on ssDNA prior to dissociation of BRCA2.
195
Similar attenuation of Rad51
ATPase activity is seen with
C. elegans
BRCA2 homolog BRC-2.
199
