title: Minimal detection of nuclear mutations in XP-V and normal cells treated with oxidative stress inducing agents.
abstract: 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.
authors.affiliation: Environmental and Molecular Toxicology Program, Department of Biological Sciences, North Carolina State University, Raleigh, NC, 27695, USA. scott_mcculloch@ncsu.edu.
authors.forename: Kimberly N
authors.initials: KN
authors.lastname: Herman
authors.forename: Shannon
authors.initials: S
authors.lastname: Toffton
authors.forename: Scott D
authors.initials: SD
authors.lastname: McCulloch
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D004249:DNA Damage; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000099270:Y-Family DNA Polymerases
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D004272:DNA, Mitochondrial; D004259:DNA-Directed DNA Polymerase; D003849:Deoxyguanosine; D017382:Reactive Oxygen Species; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases
keywords: DNA damage; DNA polymerase η; mutagenesis; oxidative stress; translesion synthesis