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Abnormal Cytokinesis in Cells Deficient in the Breast Cancer Susceptibility Protein BRCA2
Abstract
Germ-line mutations inactivating BRCA2 predispose to cancer. BRCA2-deficient cells exhibit alterations in chromosome number (aneuploidy), as well as structurally aberrant chromosomes. Here, we show that BRCA2 deficiency impairs the completion of cell division by cytokinesis. BRCA2 inactivation in murine embryo fibroblasts (MEFs) and HeLa cells by targeted gene disruption or RNA interference delays and prevents cell cleavage. Impeded cell separation is accompanied by abnormalities in myosin II organization during the late stages in cytokinesis. BRCA2 may have a role in regulating these events, as it localizes to the cytokinetic midbody. Our findings thus link cytokinetic abnormalities to a hereditary cancer syndrome characterized by chromosomal instability and may help to explain why BRCA2-deficient tumors are frequently aneuploid.
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Cited by
Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells
Fujiwara, T., Bandi, M., Nitta, M., Ivanova, E. V., Bronson, R. T., & Pellman, D. (2005) · Nature · doi:10.1038/nature04217 · Cited by 1,067
Resistance to therapy caused by intragenic deletion in BRCA2
Edwards, S. L., Brough, R., Lord, C. J., Natrajan, R., Vatcheva, R., Levine, D. A., Boyd, J., Reis-Filho, J. S., & Ashworth, A. (2008) · Nature · doi:10.1038/nature06548 · Cited by 1,011
Control of BRCA2 Cellular and Clinical Functions by a Nuclear Partner, PALB2
Xia, B., Sheng, Q., Nakanishi, K., Ohashi, A., Wu, J., Christ, N., Liu, X., Jasin, M., Couch, F. J., & Livingston, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.05.022 · Cited by 861
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
Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis
Holland, A. J., & Cleveland, D. W. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2718 · Cited by 859
Metadata
- Authors
- Daniels, M. J., Wang, Y., Lee, M., & Venkitaraman, A. R.
- Venue
- Science
- Published
- 2004-10-29
- Volume
- 306
- Issue
- 5697
- Pages
- 876-879
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1992181243
- Cited by
- 319
- References
- 0
- FWCI
- 9.85
- Type
- journal article
- Language
- en
- Open access
- closed
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- Daniels, M. J., Wang, Y., Lee, M., & Venkitaraman, A. R. (2004). Abnormal Cytokinesis in Cells Deficient in the Breast Cancer Susceptibility Protein BRCA2. Science. https://doi.org/10.1126/science.1102574
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