A Network of Genes Connects Polyglutamine Toxicity to Ploidy Control in Yeast

Overview

Journal Nat Commun

Specialty Biology

Date 2013 Mar 14

PMID 23481379

Citations 12

Authors

Christoph J O Kaiser

Stefan W Grotzinger

Julia M Eckl

Katharina Papsdorf

Stefan Jordan

Klaus Richter

Affiliations

Soon will be listed here.

Abstract

Neurodegeneration is linked to protein aggregation in several human disorders. In Huntington's disease, the length of a polyglutamine stretch in Huntingtin is correlated to neuronal death. Here we utilize a model based on glutamine stretches of 0, 30 or 56 residues in Saccharomyces cerevisiae to understand how such toxic proteins interfere with cellular physiology. A toxicity-mimicking cytostatic effect is evident from compromised colony formation upon expression of polyglutamines. Interestingly, diploid cells are insensitive to polyglutamines and haploid cells can escape cytostasis by hyperploidization. Using a genome-wide screen for genes required to obtain the cytostatic effect, we identify a network related to the budding process and cellular division. We observe a striking mislocalization of the septins Cdc10 and Shs1 in cells arrested by polyglutamines, suggesting that the septin ring may be a pivotal structure connecting polyglutamine toxicity and ploidy.

Citing Articles

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