Ultraviolet-induced dimerization of non-adjacent pyrimidines

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: is the cause of the targeted u.v.-induced −1 frameshift mutation.