Journal
CELL
Volume 136, Issue 6, Pages 1032-1043Publisher
CELL PRESS
DOI: 10.1016/j.cell.2009.02.019
Keywords
-
Categories
Funding
- NIH [GM-62653, GM-64745]
- Ministerio de Educacion y Ciencia (Spain)
- Susan G. Komen postdoctoral fellowship [PDF0707927]
- U. K. Medical Research Council
- Medical Research Council [G0600332, MC_U105359877, G0700651, G9900064] Funding Source: researchfish
- MRC [G9900064, MC_U105359877, G0700651, G0600332] Funding Source: UKRI
Ask authors/readers for more resources
The breast cancer susceptibility protein, BRCA2, is essential for recombinational DNA repair. BRCA2 delivers RAD51 to double-stranded DNA (dsDNA) breaks through interaction with eight conserved, similar to 35 amino acid motifs, the BRC repeats. Here we show that the solitary BRC4 promotes assembly of RAD51 onto single-stranded DNA (ssDNA), but not dsDNA, to stimulate DNA strand exchange. BRC4 acts by blocking ATP hydrolysis and thereby maintaining the active ATP-bound form of the RAD51-ssDNA filament. Single-molecule visualization shows that BRC4 does not disassemble RAD51-dsDNA filaments but rather blocks nucleation of RAD51 onto dsDNA. Furthermore, this behavior is manifested by a domain of BRCA2 comprising all eight BRC repeats. These results establish that the BRC repeats modulate RAD51-DNA interaction in two opposing but functionally reinforcing ways: targeting active RAD51 to ssDNA and prohibiting RAD51 nucleation onto dsDNA. Thus, BRCA2 recruits RAD51 to DNA breaks and, we propose, the BRC repeats regulate DNA-binding selectivity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available