Abnormal cytokinesis in cells deficient in the breast cancer susceptibility protein BRCA2

MJ Daniels, Y Wang, MY Lee, AR Venkitaraman - Science, 2004 - science.org
MJ Daniels, Y Wang, MY Lee, AR Venkitaraman
Science, 2004science.org
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 …
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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