Aneuploidy is most often associated with cancer and developmental defects and has recently been shown to reduce cellular fitness. Yet, an abnormal number of chromosomes is not necessarily a bad thing. Many wild yeast strains and their commercial cousins used to make bread or brew beer have adapted to their living environs by rejiggering the number of chromosomes they carry. "Euploid cells are optimized to thrive under 'normal' conditions," says Li. "In stressful environments aneuploid cells can quickly gain the upper hand when it comes to finding creative solutions to roadblocks they encounter in their environment."
After Li and her team had shown in an earlier Nature study that aneuploidy can confer a growth advantage on cells when they are exposed to many different types of stress conditions, the Stowers researchers wondered whether stress itself could increase the chromosome segregation error rate.
To find out, Chen exposed yeast cells to different chemicals that induce various types of general stress and assessed the loss of an artificial chromosome. This initial screen revealed that many stress conditions, including oxidative stress, increased the rate of chromosome loss ten to 20-fold, a rate typically observed when cells are treated with benomyl, a microtubule inhibitor that directly affects chromosome segregation.
The real surprise was radicicol, a drug that induces proteotoxic stress by inhibiting a chaperone protein, recalls Chen. "Even at a concentration that barely slows down growth, radicicol induced extremely high levels of chromosome instability within a very short period of time," he says.
Continued growth of yeast cells in the presence of radicicol led to the emergence of drug-resistant colonies that had acquired an additional copy of chromosome XV. Yeast cells pretreated briefly with radicicol to induce genomic instability also adapted more efficiently to the presence of other drugs includi
|Contact: Gina Kirchweger|
Stowers Institute for Medical Research