Structure and in vitro replication of DNA templates containing 7,8-dihydro-8-oxoadenine.
Adenine residues in DNA are oxidized under the action of ionizing radiation at the C-8 position to give 7,8-dihydro-8-oxoadenine. The formation of this lesion can be considered a cause of mutations and carcinogenesis. Oligodeoxyribonucleotides 39 and 47 bases long containing a single 7,8-dihydro-8-oxoadenine (8-hydroxyadenine) residue were synthesized by using nucleoside phosphoramidites. They were used as templates to study the copies obtained in vitro by the Klenow fragment and the thermostable Taq DNA polymerase. 7,8-Dihydro-8-oxoadenine does not block the replication and thymine is incorporated opposite the damage. The modifications of the DNA duplex conformation provoked by 7,8-dihydro-8-oxoadenine are minor. 1H-NMR spectroscopy shows that the duplex is in a B form, the sugar in a normal position in the helix and the modified base in the anti position. NMR confirms that 7,8-dihydro-8-oxoadenine exists predominantly in the keto form.
Guschlbauer
W
W
Département de Recherche Fondamentale, Centre d'Etudes Nucléaires de Grenoble, France.
Duplaa
A M
AM
Guy
A
A
Téoule
R
R
Fazakerley
G V
GV
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D001482:Base Composition; D001483:Base Sequence; D004247:DNA / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D004261:DNA Replication; D004591:Electrophoresis, Polyacrylamide Gel; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000235:genetics; D010084:Oxidation-Reduction; D011522:Protons; D013698:Templates, Genetic
D009838:Oligodeoxyribonucleotides; D011522:Protons; C002992:8-hydroxyadenine; D004247:DNA; D000225:Adenine