Zeocin induced genomic instaiblity in yeast

Yeast Saccharomyces cerevisiae has been widely used as a model system for studying physiological and pharmacological action of small-molecular drugs. Here, a heterozygous diploid S. cerevisiae strain QSS4 was generated to determine whether drugs could induce chromosomal instability by determining the frequency of mitotic recombination. In combination of a custom SNP microarray, the patterns of chromosomal instability induced by drugs could also be explored at a whole genome level in QSS4. Using this system, we found Zeocin (a member of bleomycin family) treatment resulted in hundreds-fold higher rate of genomic alterations, including aneuploidy, loss of heterozygosity (LOH), and chromosomal rearrangement.酿酒酵母（Saccharomyces cerevisiae）已被广泛用作研究小分子药物生理与药理作用的模式生物系统。本研究构建得到杂合二倍体酿酒酵母菌株QSS4，以期通过检测有丝分裂重组频率，探究药物是否可诱导染色体不稳定性。结合定制单核苷酸多态性（SNP）芯片，该实验体系还可在全基因组层面解析QSS4中药物诱导的染色体不稳定性特征。利用该体系，我们发现Zeocin（博来霉素家族成员）处理可使基因组变异率提升数百倍，变异类型涵盖非整倍体、杂合性缺失（LOH）以及染色体重排。