The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
The BRC Repeats of BRCA2 Modulate the DNA-Binding Selectivity of RAD51
Open accessAbstract
SUMMARY 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, ~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 manifest 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.
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Cites
Insights into DNA recombination from the structure of a RAD51–BRCA2 complex
Pellegrini, L., Yu, D. S., Lo, T., Anand, S., Lee, M., Blundell, T. L., & Venkitaraman, A. R. (2002) · Nature · doi:10.1038/nature01230 · Cited by 704
Self-citationRecombination Mediator and Rad51 Targeting Activities of a Human BRCA2 Polypeptide
Filippo, J. S., Chi, P., Sehorn, M. G., Etchin, J., Krejci, L., & Sung, P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601249200 · Cited by 134
Cited by
Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis
Moynahan, M. E., & Jasin, M. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2851 · Cited by 930
Homologous Recombination and Human Health: The Roles of BRCA1, BRCA2, and Associated Proteins
Prakash, R., Zhang, Y., Feng, W., & Jasin, M. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016600 · Cited by 869
Petermann, E., Orta, M. L., Issaeva, N., Schultz, N., & Helleday, T. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.01.021 · Cited by 828
Purified human BRCA2 stimulates RAD51-mediated recombination
Jensen, R. B., Carreira, A., & Kowalczykowski, S. C. (2010) · Nature · doi:10.1038/nature09399 · Cited by 715
Self-citationRad51 protects nascent DNA from Mre11-dependent degradation and promotes continuous DNA synthesis
Hashimoto, Y., Ray Chaudhuri, A., Lopes, M., & Costanzo, V. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1927 · Cited by 548
Metadata
- Authors
- Carreira, A., Hilario, J., Amitani, I., Baskin, R. J., Shivji, M. K. K., Venkitaraman, A. R., & Kowalczykowski, S. C.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 136
- Issue
- 6
- Pages
- 1032-1043
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2149326807
- Cited by
- 268
- References
- 2
- FWCI
- 8.16
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Carreira, A., Hilario, J., Amitani, I., Baskin, R. J., Shivji, M. K. K., Venkitaraman, A. R., & Kowalczykowski, S. C. (2009). The BRC Repeats of BRCA2 Modulate the DNA-Binding Selectivity of RAD51. Cell. https://doi.org/10.1016/j.cell.2009.02.019
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