Yeast: a simple model system to study complex phenomena of aneuploidy

Abstract

Aneuploidy, the state of having a chromosome number different from a multiple of the haploid number, has been associated with diseases and developmental disorders. The role of aneuploidy in human disease pathology, especially in cancer, has been a subject of much attention and debate over the last century due to the intrinsic complexity of the phenomena and experimental challenges. Over the last decade, yeast has been an invaluable model for driving discoveries about the genetic and molecular aspects of aneuploidy. The understanding of aneuploidy has been significantly improved owing to the methods for selectively generating aneuploid yeast strains without causing other genetic changes, techniques for detecting aneuploidy, and cutting-edge genetics and ‘omics’ approaches. In this review, we discuss the contribution of studies in yeast to current knowledge about aneuploidy. Special emphasis is placed on experimental features which make yeast a simpler and efficient model to investigate the complex questions in the field of aneuploidy.

Adaptive aneuploidy counters a dysregulated SUMO system

“…Previous reports have documented how specific aneuploidies may confer a selective advantage under stressful conditions. 3 Our data support an aneuploidymediated compensatory mechanism that overcomes the stress caused by a dysregulated SUMO system. These observations raise several questions for further study.…”

“…Although aneuploidy generally leads to reduces cell fitness, it can provide a rapid response to various cellular stresses, including DNA damage, gene loss, and nutrient restrictions. 3 This is thought to work by increasing the dosage of a gene or genes that help to neutralize the stress. Therefore, the duplication of entire chromosomes can yield a selective growth advantage under specific stresses.…”

Loss of the SUMO protease Ulp2 triggers a specific multichromosome aneuploidy

“…Several reports indicate that aneuploidy in yeast can be a rapid adaptation to specific types of stress (Hughes et al 2000;Gresham et al 2008;Rancati et al 2008;Pavelka et al 2010b;Yona et al 2012;Mulla et al 2014;Kaya et al 2015). In all of these examples, one particular chromosome is duplicated.…”

“…Although aneuploidy generally reduces cell fitness, aneuploidy can provide a means for quickly adapting to cellular stress or mutation (Rancati et al 2008;Mulla et al 2014;Kaya et al 2015). This selective aneuploidy is rapid compared with alternative adaptive mechanisms, such as accumulation of advantageous point mutations.…”

“…Two genes encoded on the duplicated chromosome provide enhanced resistance to FLC; one is the direct drug target and the other regulates a drug efflux system that removes the drug from cells (Selmecki et al 2008). Adaptive aneuploidies have also been observed in budding yeast and are triggered by various stressors, including DNA damage, gene deletions, and nutrient restrictions (Mulla et al 2014). The resulting aneuploidy increases the dosage of a gene or genes that help to neutralize the stress.…”