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Minimal Detection of Nuclear Mutations in XP‐V and Normal Cells Treated with Oxidative Stress Inducing Agents
Author(s) -
Herman Kimberly N.,
Toffton Shan,
McCulloch Scott D.
Publication year - 2014
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21599
Subject(s) - oxidative stress , mutagenesis , dna damage , dna polymerase , microbiology and biotechnology , dna , chemistry , nuclear dna , guanine , mutation , reactive oxygen species , dna repair , polymerase , dna replication , oxidative phosphorylation , gene , biology , mitochondrial dna , biochemistry , nucleotide
Elevated levels of reactive oxygen species (ROS) can be induced by exposure to various chemicals and radiation. One type of damage in DNA produced by ROS is modification of guanine to 7,8‐dihydro‐8‐oxoguanine (8‐oxoG). This particular alteration to the chemistry of the base can inhibit the replication fork and has been linked to mutagenesis, cancer, and aging. In vitro studies have shown that the translesion synthesis polymerase, DNA polymerase η (pol η), is able to efficiently bypass 8‐oxoG in DNA. In this study, we wanted to investigate the mutagenic effects of oxidative stress, and in particular 8‐oxoG, in the presence and absence of pol η. We quantified levels of oxidative stress, 8‐oxoG levels in DNA, and nuclear mutation rates. We found that most of the 8‐oxoG detected were localized to the mitochondrial DNA, opposed to the nuclear DNA. We also saw a corresponding lack of mutations in a nuclear‐encoded gene. This suggests that oxidative stress’ primary mutagenic effects are not predominantly on genomic DNA.