Uncovering Bleomycin-Induced Genomic Alterations and Underlying Mechanisms in the Yeast <i>Saccharomyces cerevisiae</i>
Dao-Qiong Zheng, Yu-Ting Wang, Ying-Xuan Zhu, Huan Sheng, Ke-Jing Li, Yang Sui, Ke Zhang
Abstract
Bleomycin is an antitumor antibiotic that can mutate genomic DNA. Using yeast models in combination with genome sequencing, the mutational signatures of Zeocin (a member of the bleomycin family) are disclosed. Translesion-synthesis polymerases are crucial for the viability of Zeocin-treated yeast cells at the sacrifice of a higher mutation rate. We also confirmed that multiple genomic alterations were associated with the improved resistance to Zeocin, providing novel insights into how bleomycin resistance is developed in cells.
Topics & Concepts
BiologyGeneticsSaccharomyces cerevisiaeLoss of heterozygositygenomic DNADNA damageYeastBleomycinMutationPolymeraseDNAMitotic crossoverGenomeDNA repairDNA polymeraseGenome instabilityBreakpointMolecular biologyGenePolymerase chain reactionMutagenesisDNA replicationAlleleGenotoxicityMutation ratePloidyHygromycin BPoint mutationGenomicsHomologous recombinationPyrimidine dimerMicrobial Natural Products and BiosynthesisCancer therapeutics and mechanismsSynthesis and Biological Activity