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Published Online September 16, 2004
Science DOI: 10.1126/science.1102574

Reports

Submitted on July 9, 2004
Accepted on September 7, 2004

Abnormal Cytokinesis in Cells Deficient in the Breast Cancer Susceptibility Protein BRCA2

Matthew J. Daniels 1, Yunmei Wang 1, MiYoung Lee 1, Ashok R. Venkitaraman 1*

1 University of Cambridge, Cancer Research UK, Department of Oncology and the Medical Research Council (MRC) Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, UK.

* To whom correspondence should be addressed.
Ashok R. Venkitaraman , E-mail: arv22{at}cam.ac.uk

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 by targeted gene disruption or RNA interference delays and prevents cell cleavage. Impeded cell separation is accompanied by abnormalities in myosin II organization during late stages in cytokinesis. Suggestive of a role in regulating these events, BRCA2 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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Science. ISSN 0036-8075 (print), 1095-9203 (online)