Global Analysis of Furfural-Induced Genomic Instability Using a Yeast Model
Global Analysis of Furfural-Induced Genomic Instability Using a Yeast Model
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DOI：
10.1128/aem.01237-19
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发表时间：
2019-07
影响因子：
4.4
通讯作者：
Lei S. Qi;Ke Zhang;Yu-Ting Wang;Jiankun Wu;Yang Sui;Xiaojing Liang;Lin-Zi Yu;Xuechang Wu;Pinmei Wang;Jin-Zhong Xu;Daoqiong Zheng
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文献类型：
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作者：
Lei S. Qi;Ke Zhang;Yu-Ting Wang;Jiankun Wu;Yang Sui;Xiaojing Liang;Lin-Zi Yu;Xuechang Wu;Pinmei Wang;Jin-Zhong Xu;Daoqiong Zheng
糠醛是否以及如何影响基因组完整性尚未阐明。使用酿酒酵母模型，我们发现糠醛暴露导致体内DSB和有丝分裂重组的数量级升高。总染色体重排和非整倍性事件也发生在糠醛处理的细胞中以更高的频率。在全基因组分析中，我们发现糠醛处理的细胞和野生型细胞中有丝分裂重组和点突变的模式有很大不同。摘要糠醛是一种重要的可再生化学品和燃料的前体物质，是生物乙醇发酵过程中纤维素水解产物的主要抑制剂，也是一种潜在的致癌物质。使用允许检测交叉事件的酿酒酵母中的遗传系统，我们观察到当用0.1 g/L至20 g/L糠醛处理细胞时，有丝分裂重组的频率升高1.5至40倍。与交叉事件相关的基因转换域的分析表明，大多数糠醛诱导的重组导致的DNA双链断裂（DSB）发生在G1期的修复。糠醛在体外不能直接破坏DNA，但在体内可引发与活性氧积累有关的DSB。通过全基因组单核苷酸多态性（SNP）微阵列和测序，糠醛诱导的基因组改变，范围从单碱基取代，杂合性丢失，染色体重排，非整倍体进行了探讨。在全基因组水平上，糠醛诱导的事件均匀分布在16条染色体上，但富集在高GC含量的区域。与野生型细胞相比，糠醛处理的细胞中的点突变，特别是C至T/G至A的转换显著升高。这项研究为糠醛对基因组稳定性的整体影响提供了多个新的见解。糠醛是否以及如何影响基因组完整性尚未阐明。使用酿酒酵母模型，我们发现糠醛暴露导致体内DSB和有丝分裂重组的数量级升高。总染色体重排和非整倍性事件也发生在糠醛处理的细胞中以更高的频率。在全基因组分析中，我们发现糠醛处理的细胞和野生型细胞中有丝分裂重组和点突变的模式显着不同。
Whether and how furfural affects genome integrity have not been clarified. Using a Saccharomyces cerevisiae model, we found that furfural exposure leads to in vivo DSBs and elevation in mitotic recombination by orders of magnitude. Gross chromosomal rearrangements and aneuploidy events also occurred at a higher frequency in furfural-treated cells. In a genome-wide analysis, we show that the patterns of mitotic recombination and point mutations differed dramatically in furfural-treated cells and wild-type cells. ABSTRACT Furfural is an important renewable precursor for multiple commercial chemicals and fuels; a main inhibitor existing in cellulosic hydrolysate, which is used for bioethanol fermentation; and a potential carcinogen, as well. Using a genetic system in Saccharomyces cerevisiae that allows detection of crossover events, we observed that the frequency of mitotic recombination was elevated by 1.5- to 40-fold when cells were treated with 0.1 g/liter to 20 g/liter furfural. Analysis of the gene conversion tracts associated with crossover events suggested that most furfural-induced recombination resulted from repair of DNA double-strand breaks (DSBs) that occurred in the G1 phase. Furfural was incapable of breaking DNA directly in vitro but could trigger DSBs in vivo related to reactive oxygen species accumulation. By whole-genome single nucleotide polymorphism (SNP) microarray and sequencing, furfural-induced genomic alterations that range from single base substitutions, loss of heterozygosity, and chromosomal rearrangements to aneuploidy were explored. At the whole-genome level, furfural-induced events were evenly distributed across 16 chromosomes but were enriched in high-GC-content regions. Point mutations, particularly the C-to-T/G-to-A transitions, were significantly elevated in furfural-treated cells compared to wild-type cells. This study provided multiple novel insights into the global effects of furfural on genomic stability. IMPORTANCE Whether and how furfural affects genome integrity have not been clarified. Using a Saccharomyces cerevisiae model, we found that furfural exposure leads to in vivo DSBs and elevation in mitotic recombination by orders of magnitude. Gross chromosomal rearrangements and aneuploidy events also occurred at a higher frequency in furfural-treated cells. In a genome-wide analysis, we show that the patterns of mitotic recombination and point mutations differed dramatically in furfural-treated cells and wild-type cells.