IDENTIFICATION OF ON AND OFF SIGNALING CASCADE OF MITOTIC CHECKPOINT

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 细胞通过一系列有序的事件进行繁殖，在这些事件中，细胞复制其内容物，然后一分为二。这种复制和分裂的循环称为细胞周期。在每个周期结束时，称为有丝分裂期，复制的染色体必须准确地分离到子细胞中，以忠实地传递遗传信息。这个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标志。为了确保准确的染色体分离，有丝分裂检查点被激活以阻止细胞周期进展，直到将产生丢失的染色体的错误被修复。已知有几种蛋白质在这种开启和关闭检查点信号传导中具有关键作用，尽管精确的机制仍有待进一步阐明。我在这里建议采取几种方法来破译有丝分裂检查点信号的激活，转导，沉默，以及这些错误的缺陷的后果。

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.