HVEM TOMOGRAPHY OF MITOTIC SPINDLES IN POLYPLOID YEAST

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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.