title: Critical roles for polymerase zeta in cellular tolerance to nitric oxide-induced DNA damage.
abstract: Nitric oxide (NO), a signal transmitter involved in inflammation and regulation of smooth muscle and neurons, seems to cause mutagenesis, but its mechanisms have remained elusive. To gain an insight into NO-induced genotoxicity, we analyzed the effect of NO on a panel of chicken DT40 clones deficient in DNA repair pathways, including base and nucleotide excision repair, double-strand break repair, and translesion DNA synthesis (TLS). Our results show that cells deficient in Rev1 and Rev3, a subunit essential for DNA polymerase zeta (Polzeta), are hypersensitive to killing by two chemical NO donors, spermine NONOate and S-nitroso-N-acetyl-penicillamine. Mitotic chromosomal analysis indicates that the hypersensitivity is caused by a significant increase in the level of induced chromosomal breaks. The data reveal the critical role of TLS polymerases in cellular tolerance to NO-induced DNA damage and suggest the contribution of these error-prone polymerases to accumulation of single base substitutions.
authors.affiliation: Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
authors.forename: Katsuya
authors.initials: K
authors.lastname: Takenaka
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Sonoda
authors.forename: Helfrid
authors.initials: H
authors.lastname: Hochegger
authors.forename: Shosuke
authors.initials: S
authors.lastname: Kawanishi
authors.forename: Takuo
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Yamazoe
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002645:Chickens; D002869:Chromosome Aberrations; D004249:DNA Damage; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D009569:Nitric Oxide / Q000633:toxicity*; D009713:Nucleotidyltransferases / Q000502:physiology*; D017354:Point Mutation
chemical_list: D009569:Nitric Oxide; C425929:DNA polymerase zeta; D009713:Nucleotidyltransferases; D004259:DNA-Directed DNA Polymerase