Global Analysis of Furfural-Induced Genomic Instability Using a Yeast Model
| Autor: | Xuechang Wu, Yang Sui, Jin-Zhong Xu, Xiao-Zhuan Liang, Lin-Zi Yu, Pin-Mei Wang, Yu-Ting Wang, Ke Zhang, Dao-Qiong Zheng, Lei Qi, Jian-Kun Wu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0106 biological sciences
Genome instability Mitotic crossover Saccharomyces cerevisiae Genetics and Molecular Biology medicine.disease_cause 01 natural sciences Applied Microbiology and Biotechnology Genomic Instability Loss of heterozygosity 03 medical and health sciences chemistry.chemical_compound 010608 biotechnology medicine DNA Breaks Double-Stranded Furaldehyde Gene conversion 030304 developmental biology 0303 health sciences Mutation integumentary system Ecology biology Chemistry Point mutation biology.organism_classification Cell biology Carcinogens Chromosomes Fungal Genome Fungal Cell Division DNA Food Science Biotechnology |
| Zdroj: | Applied and Environmental Microbiology. 85 |
| ISSN: | 1098-5336 0099-2240 |
| DOI: | 10.1128/aem.01237-19 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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