A major role for mitotic cdc2 kinase inactivation in the establishment of the mitotic DNA damage checkpoint
A major role for mitotic cdc2 kinase inactivation in the establishment of the mitotic DNA damage checkpoint
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DOI：
10.1158/0008-5472.can-04-1613
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发表时间：
2004-12-15
期刊：
影响因子：
11.2
通讯作者：
Amor-Guéret, M
中科院分区：
文献类型：
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作者：
Bayart, E;Grigorieva, O;Amor-Guéret, M
Cdc 2激酶在纺锤体组装检查点期间发生DNA损伤时失活。在这里，我们表明，有丝分裂布卢姆综合征蛋白磷酸化的水平反映了cdc 2活性的水平。通过引入DNA双链断裂或roscovitine处理使cdc 2完全失活，防止退出有丝分裂。因此，有丝分裂cdc 2失活在有丝分裂DNA损伤检查点的建立中起主要作用。作为对有丝分裂cdc 2失活的响应，在非恶性细胞中释放药物阻断后，M/G（1）转换延迟，而肿瘤细胞退出有丝分裂而不分裂并重新复制其DNA，这导致有丝分裂灾难。这为新的化疗策略开辟了道路。
Cdc2 kinase is inactivated when DNA damage occurs during the spindle assembly checkpoint. Here, we show that the level of mitotic Bloom syndrome protein phosphorylation reflects the level of cdc2 activity. A complete inactivation of cdc2 by either introduction of DNA double-strand breaks or roscovitine treatment prevents exit from mitosis. Thus, mitotic cdc2 inactivation plays a major role in the establishment of the mitotic DNA damage checkpoint. In response to mitotic cdc2 inactivation, the M/G(1) transition is delayed after releasing the drug block in nonmalignant cells, whereas tumor cells exit mitosis without dividing and rereplicate their DNA, which results in mitotic catastrophe. This opens the way for new chemotherapeutic strategies.