METAPHASE TO ANAPHASE TRANSITION IN MITOSIS AND MEIOSIS

描述（改编自摘要）：虽然一些进化的 已经确定了中期到后期过渡中的保守参与者， 关于后期促进复合物的调控仍然存在关键问题 (APC)，单个APC亚单位的功能，以及APC 其检查点调节因子也在减数分裂中起作用。的长期目标 这个项目是定义，在分子的细节，共享和 驱动和/或调节中期到后期的独特细胞过程 生殖细胞有丝分裂、卵母细胞减数分裂和精母细胞减数分裂过程中的过渡， 线虫C.优雅C.秀丽隐杆线虫特别适合 研究，因为可以研究有丝分裂和减数分裂中的突变缺陷 同时在一只动物身上。这项建议的具体目标是： 1)为了完成emb-27的基本分子和遗传特征分析， 生殖细胞增殖和卵母细胞增殖所需的基因， 精母细胞完成减数分裂，2）启动研究 其他基因所需的中期到后期过渡（MAT）通过 分析温度敏感突变体以及胚胎， 通过RNA介导的干扰破坏所选APC基因的表达， 对emb-27等MAT突变体的表型缺陷进行了排序， 中期到后期过渡的已知子阶段。这些研究 预计将揭示这一重要细胞中的新的和保守的参与者。 过程保守的蛋白质将直接关系到我们的理解 染色体分离的缺陷是如何导致细胞死亡，出生缺陷 和/或肿瘤进展，而非保守蛋白质可以识别新的 用于治疗线虫寄生虫感染的靶标。

DESCRIPTION (adapted from the abstract): Although several of the evolutionary conserved players in the metaphase to anaphase transition have been identified, key questions remain concerning the regulation of anaphase promoting complex (APC), the function of individual APC subunits, and the possibility that APC and its checkpoint regulators also function in meiosis. The long-term goal of this project is to define, in molecular detail, the combination of shared and unique cellular processes which drive and/or regulate the metaphase to anaphase transition during germline mitosis, oocyte meiosis, and spermatocyte meiosis in the nematode, C. elegans. C. elegans is particularly well suited for these studies since mutant defects in mitosis and meiosis can be studied simultaneously within a single animal. The specific aims of this proposal are: 1) to complete the basic molecular and genetic characterization of emb-27, a gene which is required both for germ cells to proliferate, and for oocytes and spermatocytes to complete their meiotic divisions, 2) to initiate studies of other genes required for the metaphase to anaphase transition (MAT) through the analysis of both temperature sensitive mutants as well as embryos in which the expression of selected APC genes been disrupted by RNA mediated interference, and 3) to order the phenotypic defects of emb-27 and other MAT mutants relative to known substages of the metaphase to anaphase transition. These studies are expected to reveal both novel and conserved players in this important cellular process. The conserved proteins will be directly relevant to our understanding of how defects in chromosome segregation lead to cell death, birth defects and/or tumor progression, whereas the non-conserved proteins may identify new targets for treatment of nematode parasitic infections.