Mitochondrial superoxide dismutase Sod2 suppresses nuclear genome instability during oxidative stress.
Oxidative stress can damage DNA and thereby contribute to genome instability. To avoid an imbalance or overaccumulation of reactive oxygen species (ROS), cells are equipped with antioxidant enzymes that scavenge excess ROS. Cells lacking the RecQ-family DNA helicase Sgs1, which contributes to homology-dependent DNA break repair and chromosome stability, are ... known to accumulate ROS, but the origin and consequences of this oxidative stress phenotype are not fully understood. Here, we show that the sgs1 mutant exhibits elevated mitochondrial superoxide, increased mitochondrial mass, and accumulation of recombinogenic DNA lesions that can be suppressed by antioxidants. Increased mitochondrial mass in the sgs1? mutant is accompanied by increased mitochondrial branching, which was also inducible in wildtype cells by replication stress. Superoxide dismutase Sod2 genetically interacts with Sgs1 in the suppression of nuclear chromosomal rearrangements under paraquat (PQ)-induced oxidative stress. PQ-induced chromosome rearrangements in the absence of Sod2 are promoted by Rad51 recombinase and the polymerase subunit Pol32. Finally, the dependence of chromosomal rearrangements on the Rev1/Pol ? mutasome suggests that under oxidative stress successful DNA synthesis during DNA break repair depends on translesion DNA synthesis.
Mesh Terms:
Antioxidants, DNA, Genomic Instability, Humans, Oxidative Stress, Reactive Oxygen Species, RecQ Helicases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Superoxide Dismutase
Antioxidants, DNA, Genomic Instability, Humans, Oxidative Stress, Reactive Oxygen Species, RecQ Helicases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Superoxide Dismutase
Genetics
Date: Oct. 04, 2023
PubMed ID: 37638880
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