Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues.
It has been shown previously that deoxyguanosine residues in DNA are hydroxylated at the C-8 position both in vitro and in vivo to produce 8-hydroxydeoxyguanosine (8-OH-dG) by various agents that produce oxygen radicals such as reducing reagents-O2, metal ions-O2, polyphenol-H2O2-Fe3+, asbestos-H2O2 or ionizing radiation. These agents are mostly either mutagenic or carcinogenic; therefore, the formation of 8-OH-dG can also be considered a likely cause of mutation or carcinogenesis by oxygen radicals. It is of interest to know whether the 8-OH-dG residue in DNA is misread during DNA replication. To answer this question, we have examined the effect of the 8-OH-dG residue in DNA on the fidelity of DNA replication using a DNA synthesis system in vitro with Escherichia coli DNA polymerase I (Klenow fragment). The synthetic oligodeoxynucleotides, with or without an 8-OH-dG residue in a specified position, were chemically synthesized and used as templates for DNA synthesis under the conditions of the dideoxy chain termination sequencing method. Surprisingly, in addition to misreading of the 8-OH-dG residue itself, pyrimidines next to the 8-OH-dG residue (G has not yet been tested) were also misread.
D000080242:8-Hydroxy-2'-Deoxyguanosine; D001483:Base Sequence; D004247:DNA / Q000187:drug effects / Q000235:genetics*; D004249:DNA Damage; D004261:DNA Replication; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000235:genetics; D005609:Free Radicals; D009154:Mutation; D010100:Oxygen / Q000494:pharmacology; D013698:Templates, Genetic
D005609:Free Radicals; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; D010100:Oxygen