2-Hydroxyadenine (isoguanine) as oxidative DNA damage: its formation and mutation inducibility.
In our experiments we found that hydroxylation occurs at the C-2 position of adenine by oxygen radical treatment (Fe(2+)-EDTA) of dA, dATP, and single- and double-stranded DNA. This oxidatively damaged base, 2-hydroxyadenine (also known as isoguanine), was produced more efficiently in monomers than in polynucleotides. 2-Hydroxydeoxyadenosine triphosphate was incorporated opposite T and C in a DNA template by DNA polymerase alpha and only opposite T by the Klenow fragment. The Klenow fragment, DNA polymerases alpha and beta incorporated dTMP and other nucleotides opposite 2-OH-Ade in DNA templates in vitro in a sequence-dependent manner. These results suggest that the formation of 2-OH-Ade in DNA will induce mutations in cells.
Kamiya
H
H
Department of Environmental Oncology, University of Occupational and Environmental Health, Kitakyushu, Japan.
Kasai
H
H
D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006147:Guanine / Q000737:chemistry / Q000378:metabolism*; D006900:Hydroxylation; D015394:Molecular Structure; D009154:Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D006147:Guanine; D004247:DNA; C008183:isoguanine; D004259:DNA-Directed DNA Polymerase