The Role of Separase During Cytokinesis in C elegans

描述(申请人提供)：细胞分裂的过程需要各种细胞过程的正确顺序和时间安排，以确保遗传物质和细胞内容的忠实传递。进入后期时，姐妹染色单体凝聚力被一种被称为分离酶的蛋白酶裂解。最近发现，分离酶能促进芽殖酵母的后期纺锤体动力学和胞质分裂，同时伴随着染色体的分离。我们实验室以前的研究在线虫中发现了分离酶同源物的一个温度敏感等位基因。这些分离酶突变体虫的胚胎在限制性温度下表现出一些减数分裂和有丝分裂缺陷，如染色体不分离、渗透和机械敏感性以及细胞质分裂失败。利用各种遗传学和细胞生物学技术，我建议揭示线虫早期胚胎中分离酶促进细胞质分裂完成的机制。通过这一分析，我希望扩大对染色体分离与后期和胞质分裂开始的时间协调的分子机制的理解。

DESCRIPTION (provided by applicant): The process of cell division requires the correct sequence and timing of various cellular processes to ensure faithful transmission of the genetic material and cellular contents. The entry to anaphase occurs upon the cleavage of sister-chromatid cohesion by a protease known as separase. Separase has recently been shown to promote anaphase spindle dynamics and cytokinesis concomitantly with chromosome segregation in budding yeast. Previous studies from our laboratory identified a temperature-sensitive allele of the separase homologue in C. elegans. Embryos from these separase-mutant worms shifted to the restrictive temperature display several meiotic and mitotic defects such as chromosome nondisjunction, osmotic and mechanical sensitivity, and cytokinesis failure. Using various genetic and cell biological techniques, I propose to uncover the mechanisms by which separase contributes to the completion of cytokinesis in the early embryo of C. elegans. Through this analysis, I hope to extend the understanding of the molecular mechanisms utilized for the temporal coordination of chromosome segregation with the onset of anaphase and cytokinesis.