A 2-deoxyribonolactone-containing nucleotide: isolation and characterization of the alkali-sensitive photoproduct of the trideoxyribonucleotide d(ApCpA).
It has been reported that ACA sequences in DNA are mutagenic hot spots in UV-induced mutagenesis and are sites of an alkali-sensitive lesion produced by UV irradiation. In order to characterize the UV-induced lesion of an ACA site, chemically synthesized trideoxyribonucleotide d(ApCpA) was irradiated with UV light and the alkali-sensitive photoproduct was isolated. The structure of this photoproduct was characterized as the trinucleotide containing 2-deoxyribonolactone at the internal residue by 2D DQF-COSY, FT-IR, FAB-MS, and chemical properties. It is known that this lesion is also produced by gamma-irradiation, neocarzinostatin, the 1,10-phenanthroline-copper complex, and hydrogen peroxide and is highly mutagenic because of its resistance to cleavage by certain apurinic/apyrimidinic (AP) endonucleases. Thus, 2-deoxyribonolactone may be one of the lethal DNA lesions induced by UV irradiation to organisms and one of the intermediates of UV-induced DNA strand breaks because the DNA strand is cleaved at this site with beta- and subsequent delta-elimination mechanisms.
Urata
H
H
Osaka University of Pharmaceutical Sciences, Japan.
Yamamoto
K
K
Akagi
M
M
Hiroaki
H
H
Uesugi
S
S
D001482:Base Composition; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D009838:Oligodeoxyribonucleotides / Q000302:isolation & purification*; D013400:Sugar Acids; D014466:Ultraviolet Rays
D009838:Oligodeoxyribonucleotides; D013400:Sugar Acids; C056405:2,4,5-trihydroxypentanoic acid gamma-lactone; C062545:deoxyadenylyl-(3'-5')-deoxycytidylyl-(3'-5')-deoxyadenosine