title: The effect of the 2-amino group of 7,8-dihydro-8-oxo-2'-deoxyguanosine on translesion synthesis and duplex stability.
abstract: Replication of DNA containing 7,8-dihydro-8-oxo-2'-deoxyguanosine (OxodG) gives rise to G --> T transversions. The syn-isomer of the lesion directs misincorporation of 2'-deoxyadenosine (dA) opposite it. We investigated the role of the 2-amino substituent on duplex thermal stability and in replication using 7,8-dihydro-8-oxo-2'-deoxyinosine (OxodI). Oligonucleotides containing OxodI at defined sites were chemically synthesized via solid phase synthesis. Translesion incorporation opposite OxodI was compared with 7,8-dihydro-8-oxo-2'-deoxyguanosine (OxodG), 2'-deoxyinosine (dI) and 2'-deoxyguanosine (dG) in otherwise identical templates. The Klenow exo- fragment of Escherichia coli DNA polymerase I incorporated 2'-deoxyadenosine (dA) six times more frequently than 2'-deoxycytidine (dC) opposite OxodI. Preferential translesion incorporation of dA was unique to OxodI. UV-melting experiments revealed that DNA containing OxodI opposite dA is more stable than when the modified nucleotide is opposed by dC. These data suggest that while duplex DNA accommodates the 2-amino group in syn-OxodG, this substituent is thermally destabilizing and does not provide a kinetic inducement for replication by Klenow exo-.
authors.affiliation: Department of Chemistry, Johns Hopkins University, 3400 N. Charles St, Baltimore, MD 21218, USA.
authors.forename: Natsuhisa
authors.initials: N
authors.lastname: Oka
authors.forename: Marc M
authors.initials: MM
authors.lastname: Greenberg
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000588:Amines / Q000737:chemistry; D020029:Base Pairing; D004247:DNA / Q000096:biosynthesis* / Q000737:chemistry*; D004249:DNA Damage; D004256:DNA Polymerase I / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D007288:Inosine / Q000031:analogs & derivatives* / Q000737:chemistry; D007700:Kinetics; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000096:biosynthesis / Q000138:chemical synthesis / Q000737:chemistry; D013696:Temperature
chemical_list: C498236:7,8-dihydro-8-oxo-2'-deoxyinosine; D000588:Amines; D009838:Oligodeoxyribonucleotides; D007288:Inosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D004256:DNA Polymerase I; D003849:Deoxyguanosine