DROSOPHILA GENES AFFECTING CHROMOSOME SEGREGATION

这项建议的重点是遗传和分子检查 果蝇zw 10基因。 zw 10基因的突变破坏了 在有丝分裂和雄性减数分裂细胞中染色体分离。 对ZW 10蛋白质的大部分兴趣源于其动力学特性。 有丝分裂时的定位。 私家侦探和他的合作者认为 这种蛋白质可能在介导动粒 功能，并在信号，或响应，存在或 动粒上没有张力。 zw 10基因编码一种 85 kd的蛋白质，与其他蛋白质没有显著的同源性， 已知功能。 PI提出了一系列聪明的实验 旨在阐明这种蛋白质的功能。 他特别 建议（1）使用免疫EM和RT视频显微镜， 跟踪ZW 10的时空分布， （2）研究注射抗ZW 10抗体的后果 （3）测定ZW 10对小鼠的作用 激光手术改变染色体张力的分布 （4）确定是否修改 ZW 10蛋白的磷酸化与其 细胞周期中的运动;（5）执行结构/功能 （6）研究ZW 10蛋白在大肠杆菌中的功能， 秀丽隐杆线虫。(7)研究ZW 10与 其他已知基因的产物;（8）识别与其他已知基因相互作用的蛋白质 通过现在标准的生物化学和遗传学手段与ZW 10杂交;以及 (9)开始对一个新基因san进行分子分析， 蛋白质产品似乎在姐妹中发挥着重要作用， 染色单体凝聚力

This proposal is focused on the genetic and molecular examination of the Drosophila zw10 gene. Mutants in the zw10 gene disrupt chromosome segregation in both mitotic and male meiotic cells. Much of the interest in the ZW10 protein stems from its dynamic localization during mitosis. The PI and his collaborators argue that this protein may play a critical role in mediating kinetochore function and in signaling, or responding to, the presence or absence of tension on the kinetochore. The zw10 gene encodes an 85 kd protein with no significant homologies to other proteins of known function. The PI proposes a clever set of experiments designed to elucidate the function of this protein. Specifically, he proposes to (1) use immuno-EM and RT videomicroscopy to follow the temporal and spatial distribute of ZW10 at very high resolution; (2) investigate the consequences of injecting anti-ZW10 antibodies at various times; (3) assay the effects on ZW10 distribution of altering tension on chromosomes by Iaser surgery and by micro-manipulation; (4) determine whether modifications of the ZW10 protein (e.g. phosphorylation) are associated with its movements during the cell cycle; (5) perform a structure/function dissection of ZW10; (6) study the function of the ZW10 protein in C elegans.; (7) investigate the relationship of ZW10 to the products of other known genes; (8) identify proteins that interact with ZW10 by now standard biochemical and genetic means; and (9) begin the molecular analysis of a new gene, san, whose protein product appears to play an essential role in sister chromatid cohesion.