Effects of oxidative stress on mitotic recombination and genomic stability in yeast after 20 passages

Oxidative stress is a common factor threatening genomic stability in almost all aerobic organisms. Using a yeast screening system, we measured the frequency of mitotic recombination was greatly elevated after H2O2 treatment. H2O2 was able to break chromatid directly in G1 synchronized cells and homologous recombination was induced to repair DNA double stand breaks at S/G2 phase. By whole genome SNP microarray and sequencing, the patterns of H2O2 induced loss of heterozygosity (LOH; gene conversion and crossover), chromosomal rearrangement, and aneuploidy changes were revealed. LOH events were the most common genomic alterations induced by H2O2 and were randomly distributed throughout the genome.氧化应激是几乎所有需氧生物中威胁基因组稳定性的常见诱因。本研究采用酵母筛选系统开展检测，发现经过氧化氢（H₂O₂）处理后，有丝分裂重组频率显著升高。过氧化氢可直接断裂G1期同步化细胞内的染色单体，并在S/G2期诱导同源重组以修复DNA双链断裂。通过全基因组单核苷酸多态性（Single Nucleotide Polymorphism, SNP）微阵列及测序技术，我们揭示了过氧化氢诱导的杂合性缺失（Loss of Heterozygosity, LOH，涵盖基因转换与交叉互换）、染色体重排及非整倍体改变的特征模式。其中，杂合性缺失事件是过氧化氢诱导的最常见基因组变异，且在全基因组范围内呈随机分布。