Opposing roles of Y-family DNA polymerases in lipid peroxide mutagenesis at the hisG46 target in the Ames test

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis Vol. 829-830; pp. 43 - 49
• Main Authors: Grúz, Petr, Shimizu, Masatomi, Yamada, Masami, Sugiyama, Kei-ichi, Honma, Masamitsu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2018
• Subjects: Ames test; Lipid peroxide; Y-family DNA polymerase; Ames test; Lipid peroxide; Y-family DNA polymerase
• ISSN: 1383-5718; 1879-3592
• DOI: 10.1016/j.mrgentox.2018.04.003

•DNA PolV is essential for lipid peroxide induced base substitutions in the Ames test.•New strain YG9028 could substitute for the strain TA100 in the Ames test.•DNA PolIV is protecting genomes from lipoxidative stress. DNA polymerases play a key role in mutagenesis by performing translesion DNA synthesis (TLS). The Y-family of DNA polymerases comprises several evolutionarily conserved families, specializing in TLS of different DNA adducts. Exocyclic etheno and propano DNA adducts are among the most common endogenous DNA lesions induced by lipid peroxidation reactions triggered by oxidative stress. We have investigated the participation of two enterobacterial representatives of the PolIV and PolV branches of Y-family DNA polymerases in mutagenesis by two model lipid peroxidation derived genotoxins, glyoxal and crotonaldehyde. Mutagenesis by the ethano adduct (glyoxal-derived) and the propano adduct (crontonaldehyde-derived) at the GC target in the Ames test depended exclusively on PolV type DNA polymerases such as PolRI. In contrast, PolIV suppressed glyoxal and, even more, crotonaldehyde mutagenesis, as detected by enzyme overexpression and gene knockout approaches. We propose that DNA polymerase IV, which is the mammalian DNA polymerase κ ortholog, acts as a housekeeper protecting the genome from lipoxidative stress.