Genome-wide analysis of genomic alterations induced by oxidative DNA damage in yeast
Genome-wide analysis of genomic alterations induced by oxidative DNA damage in yeast
复制标题
酵母氧化 DNA 损伤引起的基因组改变的全基因组分析
DOI：
10.1093/nar/gkz027
复制
发表时间：
2019-04-23
影响因子：
14.9
通讯作者：
Petes，Thomas D.
中科院分区：
文献类型：
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作者：
Zhang，Ke;Zheng，Dao-Qiong;Petes，Thomas D.
DNA氧化损伤是对基因组稳定性的威胁。利用酵母的遗传系统检测有丝分裂重组，我们发现当细胞用过氧化氢（H2O2）处理时，交叉的频率大大提高。利用微阵列分析和基因组测序的结合，我们绘制了有丝分裂重组事件和其他染色体重排的断点，分辨率约为1kb。基因转换和交叉是最常见的两种类型的事件，但我们也观察到缺失，重复和染色体非整倍体。此外，h2o2处理的细胞有更高的点突变率（特别是A到T/T到A和C到G/G到C的转换）和小的插入/缺失（In /del）。在经过多轮H2O2处理的细胞中，我们发现了一种基因改变，通过扩增编码胞质过氧化氢酶t的CTT1基因来提高H2O2耐受性。最后，我们发现在缺氧条件下生长的细胞重组水平降低。这项研究为氧化应激如何影响有氧细胞的基因组不稳定性和表型进化提供了多种新的见解。
Abstract Oxidative DNA damage is a threat to genome stability. Using a genetic system in yeast that allows detection of mitotic recombination, we found that the frequency of crossovers is greatly elevated when cells are treated with hydrogen peroxide (H2O2). Using a combination of microarray analysis and genomic sequencing, we mapped the breakpoints of mitotic recombination events and other chromosome rearrangements at a resolution of about 1 kb. Gene conversions and crossovers were the two most common types of events, but we also observed deletions, duplications, and chromosome aneuploidy. In addition, H2O2-treated cells had elevated rates of point mutations (particularly A to T/T to A and C to G/G to C transversions) and small insertions/deletions (in/dels). In cells that underwent multiple rounds of H2O2 treatments, we identified a genetic alteration that resulted in improved H2O2 tolerance by amplification of the CTT1 gene that encodes cytosolic catalase T. Lastly, we showed that cells grown in the absence of oxygen have reduced levels of recombination. This study provided multiple novel insights into how oxidative stress affects genomic instability and phenotypic evolution in aerobic cells.