Dissection of the mitotic checkpoint component BUBR1

描述（由申请人提供）： 真核生物已经进化出一个“有丝分裂检查点”来监测中期-后期的转换，以确保遗传信息向子细胞的高保真传输。在每个着丝粒附着到有丝分裂纺锤体的微管之前，该检查点阻止通过有丝分裂的进展。在试图确定检查点信号传导如何与微管附着相关联时，克利夫兰实验室的早期工作提出，着丝粒结合的微管马达CENP-E是提供微管附着的一个环节，将其传递给着丝粒结合的检查点激酶BUBR 1。该提案的重点是测试CENP-E参与连接脊椎动物检查点微管附着的模型，重点是体外操纵细胞周期的能力（使用非洲爪蟾卵提取物）。

DESCRIPTION (provided by applicant): Eukaryotic organisms have evolved a "mitotic checkpoint" to monitor the metaphase-anaphase transition in order to assure high fidelity transmission of genetic information to daughter cells. This checkpoint prevents progression through mitosis prior to attachment of every centromere to microtubules of the mitotic spindle. In attempting to identify how checkpoint signaling is linked to microtubule attachment, earlier work from the Cleveland lab has proposed that the centromere- bound microtubule motor CENP-E is one link which provides microtubule attachment, relaying this to the centromere-bound checkpoint kinase BUBR1. The focus of this proposal is to test this model for CENP-E involvement in linking the vertebrate checkpoint to microtubule attachment, focusing on the ability to manipulate the cell cycle in vitro (using Xenopus egg extracts).