Abnormal cytokinesis in cells deficient in the breast cancer susceptibility protein BRCA2
Abnormal cytokinesis in cells deficient in the breast cancer susceptibility protein BRCA2
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DOI：
10.1126/science.1102574
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发表时间：
2004-10-29
期刊：
影响因子：
56.9
通讯作者：
Venkitaraman, AR
中科院分区：
文献类型：
--
作者：
Daniels, MJ;Wang, YM;Venkitaraman, AR
使BRCA2失活的生殖系突变易患癌症。BRCA2缺陷细胞表现出染色体数目的改变（非整倍性），以及结构异常的染色体。在这里，我们表明，BRCA2缺陷损害细胞分裂的胞质分裂的完成。BRCA2在鼠胚胎成纤维细胞（MEF）和HeLa细胞中的失活通过靶向基因破坏或RNA干扰延迟并阻止细胞分裂。在胞质分裂的晚期，细胞分离受阻伴随着肌球蛋白II组织的异常。BRCA2可能在调节这些事件中起作用，因为它定位于细胞动力学中间体。因此，我们的发现将细胞动力学异常与以染色体不稳定为特征的遗传性癌症综合征联系起来，并可能有助于解释为什么BRCA 2缺陷型肿瘤经常是非整倍体。
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.