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Chromosome Instability and Defective Recombinational Repair in Knockout Mutants of the Five Rad51 Paralogs
Open accessAbstract
The Rad51 protein, a eukaryotic homologue of Escherichia coli RecA, plays a central role in both mitotic and meiotic homologous DNA recombination (HR) in Saccharomyces cerevisiae and is essential for the proliferation of vertebrate cells. Five vertebrate genes, RAD51B, -C, and -D and XRCC2 and -3, are implicated in HR on the basis of their sequence similarity to Rad51 (Rad51 paralogs). We generated mutants deficient in each of these proteins in the chicken B-lymphocyte DT40 cell line and report here the comparison of four new mutants and their complemented derivatives with our previously reported rad51b mutant. The Rad51 paralog mutations all impair HR, as measured by targeted integration and sister chromatid exchange. Remarkably, the mutant cell lines all exhibit very similar phenotypes: spontaneous chromosomal aberrations, high sensitivity to killing by cross-linking agents (mitomycin C and cisplatin), mild sensitivity to gamma rays, and significantly attenuated Rad51 focus formation during recombinational repair after exposure to gamma rays. Moreover, all mutants show partial correction of resistance to DNA damage by overexpression of human Rad51. We conclude that the Rad51 paralogs participate in repair as a functional unit that facilitates the action of Rad51 in HR.
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Cites
Homology-directed repair is a major double-strand break repair pathway in mammalian cells
Liang, F., Han, M., Romanienko, P. J., & Jasin, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.5172 · Cited by 649
Sung, P. (1997) · Genes & Development · doi:10.1101/gad.11.9.1111 · Cited by 540
Cited by
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Bunting, S. F., Callén, E., Wong, N., Chen, H.-T., Polato, F., Gunn, A., Bothmer, A., Feldhahn, N., Fernandez-Capetillo, O., Cao, L., et al. (2010) · Cell · doi:10.1016/j.cell.2010.03.012 · Cited by 1,671
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
Meindl, A., Hellebrand, H., Wiek, C., Erven, V., Wappenschmidt, B., Niederacher, D., Freund, M., Lichtner, P., Hartmann, L., Schaal, H., et al. (2010) · Nature Genetics · doi:10.1038/ng.569 · Cited by 743
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
Repair of DNA interstrand cross-links
Dronkert, M. L. G., & Kanaar, R. (2001) · Mutation Research/DNA Repair · doi:10.1016/s0921-8777(01)00092-1 · Cited by 555
Metadata
- Authors
- Takata, M., Sasaki, M. S., Tachiiri, S., Fukushima, T., Sonoda, E., Schild, D., Thompson, L. H., & Takeda, S.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2001-04-01
- Volume
- 21
- Issue
- 8
- Pages
- 2858-2866
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2142729720
- Cited by
- 523
- References
- 2
- FWCI
- 14.66
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Takata, M., Sasaki, M. S., Tachiiri, S., Fukushima, T., Sonoda, E., Schild, D., Thompson, L. H., & Takeda, S. (2001). Chromosome Instability and Defective Recombinational Repair in Knockout Mutants of the Five Rad51 Paralogs. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.21.8.2858-2866.2001
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