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Ca 2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity
Open accessAbstract
Human Rad51 (hRad51) protein plays a key role in homologous recombination and DNA repair. hRad51 protein forms a helical filament on single-stranded DNA (ssDNA), which performs the basic steps of homologous recombination: a search for homologous double-stranded DNA (dsDNA) and DNA strand exchange. hRad51 protein possesses DNA-dependent ATPase activity; however, the role of this activity has not been understood. Our current results show that Ca 2+ greatly stimulates DNA strand exchange activity of hRad51 protein. We found that Ca 2+ exerts its stimulatory effect by modulating the ATPase activity of hRad51 protein. Our data demonstrate that, in the presence of Mg 2+ , the hRad51-ATP-ssDNA filament is quickly converted to an inactive hRad51-ADP-ssDNA form, due to relatively rapid ATP hydrolysis and slow dissociation of ADP. Ca 2+ maintains the active hRad51-ATP-ssDNA filament by reducing the ATP hydrolysis rate. These findings demonstrate a crucial role of the ATPase activity in regulation of DNA strand exchange activity of hRad51 protein. This mechanism of Rad51 protein regulation by modulating its ATPase activity is evolutionarily recent; we found no such mechanism for yeast Rad51 (yRad51) protein.
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Cites
The versatility and universality of calcium signalling
Berridge, M. J., Lipp, P., & Bootman, M. D. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35036035 · Cited by 5,701
Cited by
Regulation of Homologous Recombination in Eukaryotes
Heyer, W.-D., Ehmsen, K. T., & Liu, J. (2010) · Annual Review of Genetics · doi:10.1146/annurev-genet-051710-150955 · Cited by 1,066
Homologous recombination and the repair of DNA double-strand breaks
Wright, W. D., Shah, S. S., & Heyer, W.-D. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.tm118.000372 · Cited by 713
Human BRCA2 protein promotes RAD51 filament formation on RPA-covered single-stranded DNA
Liu, J., Doty, T., Gibson, B., & Heyer, W.-D. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1904 · Cited by 401
RTEL1 Maintains Genomic Stability by Suppressing Homologous Recombination
Barber, L. J., Youds, J. L., Ward, J. D., McIlwraith, M. J., O'Neil, N. J., Petalcorin, M. I. R., Martin, J. S., Collis, S. J., Cantor, S. B., Auclair, M., et al. (2008) · Cell · doi:10.1016/j.cell.2008.08.016 · Cited by 369
Sommers, J. A., Rawtani, N., Gupta, R., Bugreev, D. V., Mazin, A. V., Cantor, S. B., & Brosh, R. M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m809019200 · Cited by 112
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Metadata
- Authors
- Bugreev, D. V., & Mazin, A. V.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-06-28
- Volume
- 101
- Issue
- 27
- Pages
- 9988-9993
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2154074565
- Cited by
- 245
- References
- 1
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- green
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- Bugreev, D. V., & Mazin, A. V. (2004). Ca 2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0402105101
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