DROSOPHILA GENES AFFECTING CHROMOSOME SEGREGATION

我们一直在研究果蝇的基因， 这是有丝分裂过程中染色体精确分离所必需的。 突变 我们正在研究的三个基因中， 有时含有数百条染色体的多倍体细胞。 多倍体 后期的数字观察，表明这些产品的 基因在后期活动中发挥作用，我们认为这是胞质分裂。 包含所有三个基因的基因组区域已经被克隆;我们 建议继续进行这些调查，以查明和 对适当的转录单位进行测序， 用于将来的免疫定位 问题研究 将作出巨大努力，以促进我们对 第四个基因，l（1）zw 10，突变导致大的非整倍体， 在许多类型的有丝分裂组织中细胞的比例。 我们的细胞学 突变体的特征表明L（1）zw 10蛋白是 这是在分裂后期开始时正确分离姐妹染色单体所必需的。 我们 已经进一步表明，编码的蛋白质的细胞内定位 由L（1）zw 10经历了几个显着的转变过程中， 细胞周期 特别是，它位于动粒上或附近 微管在中期，但随后迅速重新分配到 后期开始时的着丝粒。 本提案中概述的实验旨在探索 l（1）zw 10乘积的可能函数。 我们会问， 蛋白质是任何染色体移动到中期板所必需的， 确定它是否参与了系统渲染后期开始 依赖于主轴的完整性，并进一步调查令人困惑的方面 这可能提供有关其功能作用的线索。 我们 我还打算研究蛋白质的结构， 超微结构水平，并确定如何新的细胞内 实现了蛋白质向这些结构的分布。 检查其他有丝分裂和减数分裂突变对细胞周期的影响。 l（1）zw 10抗原的定位可阐明基因相互作用 本地化模式以及其他方面都需要 染色体分离 最后，利用我们现有的试剂 产生，其他重要的有丝分裂细胞器的组成部分，其中 将识别L（1）ZW 10产品残留物。

We have been investigating genes in Drosophila melanogaster that are required for accurate chromosome segregation during mitosis. Mutations in three of the genes we are studying result in the appearance of highly polyploid cells sometimes containing hundreds of chromosomes. Polyploid anaphase figures are observed, suggesting that the products of these genes function in a post-anaphase event we believe to be cytokinesis. The genomic regions containing all three genes have been cloned; we propose to continue these investigations so as to identify and to sequence the proper transcriptional units, and to generate antibodies against the corresponding gene products for future immunolocalization studies. A strong effort will be made to advance our understanding of the role of a fourth gene, l(1)zw10, mutations in which cause aneuploidy in a large proportion of cells in many types of mitotic tissues. Our cytological characterization of mutants suggests that the l(1)zw10 protein is required for proper sister chromatid separation at anaphase onset. We have further shown that the intracellular location of the protein encoded by l(1)zw10 undergoes several remarkable transitions in the course of the cell cycle. In particular, it resides on or near kinetochore microtubules at metaphase, but is then rapidly redistributed to the kinetochores at the beginning of anaphase. The experiments outlined in this proposal are designed to explore possible function of the l(1)zw10 product. We will ask whether this protein is required for any chromosome movements to the metaphase plate, determine whether it participates in the system rendering anaphase onset dependent on spindle integrity, and further investigate puzzling aspects of the phenotype that may provide clues about its functional role. We also intend to study the structures in which the protein is found at the ultrastructural level, and to determine how the novel intracellular distributions of the protein to these structures are achieved. Examination of the effects of other mitotic and meiotic mutations on the localization of the l(1)zw10 antigen may illuminate gene interactions required both for the localization pattern as well as other aspects of chromosome segregation. Finally, by exploiting the reagents we have generated, other components of the important mitotic organelles in which the l(1)zw10 product reside will be identified.