Ultraviolet-induced dimerization of non-adjacent pyrimidines. A potential mechanism for the targeted -1 frameshift mutation.
The DNA photoproduct responsible for the ultraviolet (u.v.)-induced targeted -1 frameshift mutation is unknown. Based on mutagenesis studies by others, we surmised that this lesion might be found in high abundance in single-stranded DNA. u.v. irradiation of the single-stranded alternating copolymer poly[d(G-T)] yielded a photoproduct that was characterized in detail. It consists of a thymine-thymine cyclobutane dimer of predominantly cis-syn configuration occurring between non-adjacent thymidyl residues on the same strand. Its formation is strongly inhibited in double-stranded DNA. A similar u.v. photoproduct was obtained in higher yield from the polypyrimidine alternating copolymer poly[d(C-T)] under conditions in which it is single-stranded. It is proposed that replication across the unrepaired photoproduct: (formula; see text) is the cause of the targeted u.v.-induced -1 frameshift mutation.
Nguyen
H T
HT
Department of Pathology, F. E. Herbert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Minton
K W
KW
D002855:Chromatography, Thin Layer; D004307:Dose-Response Relationship, Radiation; D009154:Mutation; D009690:Nucleic Acid Conformation; D011089:Polydeoxyribonucleotides / Q000528:radiation effects; D011740:Pyrimidine Dimers / Q000528:radiation effects*; D014466:Ultraviolet Rays
D011089:Polydeoxyribonucleotides; D011740:Pyrimidine Dimers; C045717:poly d(C-T); C017650:polydeoxy(guanine-thymine) nucleotide