Global Analysis of Furfural-Induced Genomic Instability Using a Yeast Model

Area of Science:

• Biochemistry
• Genetics
• Molecular Biology

Background:

• Furfural is a key renewable chemical precursor and a known inhibitor in bioethanol fermentation.
• Its potential impact on genome integrity has remained largely uncharacterized.
• Understanding furfural's genotoxicity is crucial for its industrial applications and safety assessments.

Purpose of the Study:

• To investigate the effects of furfural on genomic stability in *Saccharomyces cerevisiae*.
• To elucidate the mechanisms underlying furfural-induced DNA damage and recombination.
• To characterize the spectrum of genome-wide alterations caused by furfural exposure.

Main Methods:

• Utilized a *Saccharomyces cerevisiae* genetic system to detect mitotic recombination events.
• Quantified recombination frequencies following furfural treatment across a range of concentrations.
• Employed whole-genome SNP microarray and sequencing to identify various genomic alterations.
• Investigated *in vitro* DNA-breaking activity and *in vivo* reactive oxygen species (ROS) accumulation.

Main Results:

• Furfural treatment (0.1–20 g/liter) elevated mitotic recombination rates by 1.5- to 40-fold.
• Furfural induced DNA double-strand breaks (DSBs) *in vivo*, primarily in the G1 phase, linked to ROS accumulation.
• Genome-wide analysis revealed increased single base substitutions (especially C-to-T/G-to-A), loss of heterozygosity, chromosomal rearrangements, and aneuploidy.
• These alterations were distributed across chromosomes and enriched in high-GC-content regions.

Conclusions:

• Furfural exposure demonstrably compromises genomic stability in yeast.
• The compound triggers *in vivo* DSBs and significantly enhances mitotic recombination and point mutations.
• Furfural poses a genotoxic risk, necessitating careful consideration in biotechnological processes and safety evaluations.