Investigate the molecular mechanism that ensures chromosome bipolar attachment

描述（由申请人提供）： 项目概要/摘要：准确的染色体分离取决于双极附着的建立，即姐妹动粒从相反的纺锤体极附着到微管上。双极连接的失败将产生非整倍体细胞，这直接导致遗传疾病，如癌症和出生缺陷。不正确的染色体附着被纺锤体组装检查点（SAC）检测到，其延迟后期开始以允许错误校正。一旦细胞建立了染色体双极附着，检查点必须沉默以允许后期开始，但对SAC沉默的分子机制知之甚少。本申请的目的是揭示和表征SAC沉默网络（SSN）。我们假设，SSN协调错误感知，纠错，和SAC沉默，以确保染色体双极附着在后期发病之前。这个提议是创新的，因为它将揭示对忠实的染色体分离至关重要的不良的未表征的信号级联SSN。本研究的完成将为SAC的消声过程提供第一个详细的视图。这项研究将是 这是因为SSN中确定的新成分将揭示癌症诊断和预防的新靶点。

DESCRIPTION (provided by applicant): Project Summary/Abstract: Accurate chromosome segregation depends on the establishment of bipolar attachment, whereby sister kinetochores are attached to microtubules from opposite spindle poles. Failure of bipolar attachment will generate aneuploid cells, which directly contributes to genetic disorders, such as cancer and birth defects. Incorrect chromosome attachments are sensed by the spindle assembly checkpoint (SAC) that delays anaphase onset to allow error-correction. Once cells have established chromosome bipolar attachments, the checkpoint has to be silenced to allow anaphase onset, but little is known about the molecular mechanism for SAC silencing. The objective of this application is to uncover and characterize the SAC silencing network (SSN). We hypothesize that the SSN coordinates error sensing, error-correction, and SAC silencing to ensure chromosome bipolar attachment prior to anaphase onset. This proposal is innovative as it will uncover the poorly uncharacterized signaling cascade SSN that is critical for faithful chromosome segregation. The completion of this research will provide the first detailed view for SAC silencing process. This research will be significant because the identified new components in the SSN will uncover new targets for cancer diagnosis and prevention.