Abstract #17

Genome-wide analysis of polyploidy in yeast: scaling effects, chromosome segregation and genome stability. Zuzana Storchova¹, Kendra Burbank², Amanda Breneman¹, Jessica Cande¹, Joshua Dunn¹, David Pellman¹. 1) Dept Ped Oncol, Dana-Farber Cancer Inst, Boston, MA., USA; 2) Dept of Physics, Harvard University, Boston, MA, USA.
   Polyploidy occurs during development, cellular stress, disease, and evolution. Despite its prevalence, little is known about the physiological alterations that accompany polyploidy. We 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. Here, we report a genome-wide screen to identify ploidy-specific lethal functions. Only 39 in 3540 mutations screened exhibited ploidy-specific lethality. Almost all of these mutations affect genomic stability by impairing homologous recombination, sister chromatid cohesion, or mitotic spindle function. We uncovered defects in wild-type tetraploids predicted by the screen and identified mechanisms by which tetraploidization affects genomic stability. We show that tetraploids have a high incidence of syntelic/monopolar kinetochore attachments to the spindle pole and our computational model suggests that this defect can be explained by scaling effects. Thus, geometric constraints may have profound effects on genome stability; the mechanisms described here may be relevant in a variety of biological contexts, including disease states such as cancer.

Return to YGM 2006 Home at SGD