HVEM TOMOGRAPHY OF MITOTIC SPINDLES IN POLYPLOID YEAST

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。多倍体发生在发育、细胞胁迫、疾病和进化过程中。尽管多倍体很普遍，但人们对多倍体伴随的生理变化知之甚少。佩尔曼实验室之前描述了一种倍性特有的致死性，即在单倍体或二倍体萌芽酵母中不致死的基因缺失会导致三倍体或四倍体的致命性。全基因组筛选被用来鉴定倍性特有的致死功能。在3540个突变筛查中，只有39个显示出倍体特有的致死性。几乎所有这些突变都通过损害同源重组、姐妹染色单体凝聚力或有丝分裂纺锤体功能来影响基因组的稳定性。Pellman实验室最近的实验表明，四倍体在纺锤体极上有很高的同轴/单极动粒附着。一个计算模型表明，这种缺陷可以用标度效应来解释。对四倍体纺锤体的连续切片、双轴断层扫描显示，纺锤体极体内斑的面积比二倍体细胞的面积大一倍，但不同倍性纺锤体的微管长度相似。因此，几何约束可能会对基因组稳定性产生深远的影响。这部作品已提交出版。

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. Polyploidy occurs during development, cellular stress, disease and evolution. Despite its prevalence, little is known about the physiological alterations that accompany polyploidy. The Pellman lab previously described ¿ploidy-specific lethality¿ where a gene deletion that is not lethal in haploid or diploid budding yeast causes lethality in triploids or tetraploids. A genome-wide screen was used to identify ploidy-specific lethal functions. Only 39 in 3540 mutations screens exhibited ploidy-specific lethality. Almost all of these mutations affect genomic stability by impairing homologous recombination, sister chromatid cohesion, or mitotic spindle function. Recent experiments in the Pellman lab show that tetraploids have a high incidence of syntelic/monopolar kinetochore attachments to the spindle pole. A computational model suggests that this defect can be explained by scaling effects. Serial section, dual-axis tomography of forming spindles in tetraploids showed that the surface of the inner plaque of the spindle pole body doubles in area relative to diploid cells, but that microtubule lengths are similar in spindles of different ploidy. Thus, geometric constraints may have profound effects on genome stability. This work has been submitted for publication.