IDENTIFICATION OF ON AND OFF SIGNALING CASCADE OF MITOTIC CHECKPOINT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 细胞通过执行有序的事件序列进行复制，在该序列中复制其内容，然后将其一分为二。这种复制和分裂的周期被称为细胞周期。在每个周期的末尾，称为有丝分裂期，复制的染色体必须被准确地分离到子细胞，以忠实地传递遗传信息。这一过程中的错误会导致染色体数量异常，这是人类肿瘤进展的一个标志。为了确保准确的染色体分离，激活有丝分裂检查点以阻止细胞周期进展，直到修复可能产生丢失染色体的错误。已知有几种蛋白质在这种开关检查点信号中起着关键作用，尽管确切的机制仍有待进一步阐明。我在这里提出了几种方法来破译有丝分裂检查点信号的激活、转导、沉默以及这些过程中每一个错误造成的缺陷的后果。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A cell reproduces by performing an orderly sequence of events in which it duplicates its contents and then divides in two. This cycle of duplication and division is called the cell cycle. At the end of each cycle, called mitotic phase, duplicated chromosomes must be accurately segregated to daughter cells for faithful transmission of genetic information. Errors in this process cause an abnormal number of chromosomes, a hallmark of human tumor progression. In order to assure accurate chromosome segregation, the mitotic checkpoint is activated to arrest cell cycle progression until errors that would generate a lost chromosome have been fixed. Several proteins are known to have pivotal roles in this on and off checkpoint signaling, although the precise mechanisms remains to be further elucidated. I propose here to pursue several approaches to deciphering mitotic checkpoint signal activation, transduction, silencing, and the consequences of deficits from errors in each of these.