title: Base recognition abilities of 2'-deoxynucleoside N-oxide derivatives and their substrate specificity in enzyme reaction.
abstract: The main products obtained by oxidation of cytosine and adenine bases with hydrogen peroxide are cytosine and adenine N-oxide derivatives. There is a possibility that these N-oxide derivatives are mutagenic in genomic DNA, such as 8-oxoguanine or thymine glycol. Although the chemical synthesis and properties of 2'-deoxynucleoside N-oxide derivatives have been well established, little has been reported about the chemical and biochemical behavior of DNA oligomers containing these modified 2'-deoxynucleoside. In this study, we examined their base recognition ability by T(m) experiments and computer modeling, and their substrate specificity in enzyme reaction. It was found that the T(m) values of in DNA-DNA, DNA-RNA duplexes incorporating 2'-deoxynucleoside N-oxide derivatives were significant low, while the one-point incorporation of these modified derivatives into the 3'-terminal site of a DNA oligomer by DNA polymerase occurred accurately selecting the complementary G or T base on a template DNA oligomer.
authors.affiliation: Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Midoriku, Yokohama, 226-8501, Japan.
authors.forename: Hirosuke
authors.initials: H
authors.lastname: Tsunoda
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kudo
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohkubo
authors.forename: Kohji
authors.initials: K
authors.lastname: Seio
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Sekine
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D020029:Base Pairing; D003497:Cyclic N-Oxides / Q000737:chemistry*; D004249:DNA Damage; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: C522091:2'-deoxycytidine-N-oxide; D003497:Cyclic N-Oxides; D009838:Oligodeoxyribonucleotides; D003841:Deoxycytidine; C030755:adenine-N-oxide; D004259:DNA-Directed DNA Polymerase; D000225:Adenine