Mutagenic properties of the T-C cyclobutane dimer

Abstract

G x C-->A x T transitions within T-C or C-C bipyrimidine sequences are by far the most frequent class of mutation induced by 254-nm UV irradiation in most genes and species investigated, but the reason for the high degree of mutability and specificity at these sites is uncertain. Some data implicate the deamination of cytosine to uracil as a possible cause, but other results appear to indicate that the rate of deamination is too low for this to be significant in Escherichia coli. If deamination is not the cause, the high degree of mutability must presumably reflect the inherent properties of T-C and C-C dimers. We investigated this question by transfecting excision-deficient and excision-proficient strains of E. coli with single-stranded vectors that carried a site-specific cis-syn T-C cyclobutane dimer and by analyzing the nucleotide sequences of replicated vector products. We found that replication past the T-C dimer, like replication past its T-T and U-U counterparts, is in fact >95% accurate and that the frequencies of bypass are also very similar for these photoproducts. Since the T-C dimer appears to be only weakly mutagenic, the high frequency of UV-induced mutations at T-C sites presumably depends on some other process, such as deamination, although the mechanism remains to be established.