TY - JOUR
T1 - A network of genes connects polyglutamine toxicity to ploidy control in yeast
AU - Kaiser, Christoph J.O.
AU - Grötzinger, Stefan W.
AU - Eckl, Julia M.
AU - Papsdorf, Katharina
AU - Jordan, Stefan
AU - Richter, Klaus
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84875884218&partnerID=8YFLogxK
U2 - 10.1038/ncomms2575
DO - 10.1038/ncomms2575
M3 - Article
C2 - 23481379
AN - SCOPUS:84875884218
SN - 2041-1723
VL - 4
JO - Nature Communications
JF - Nature Communications
M1 - 1571
ER -
