Mechanism of SOS mutagenesis of UV-irradiated DNA: Mostly error-free processing of deaminated cytosine

Abstract

We measured the kinetics of growth and mutagenesis of UV-irradiated DNA of phages S13 and λ that were undergoing SOS repair; the kinetics strongly suggest that most of SOS mutagenesis arises from the deamination of cytosine in cyclobutane pyrimidine dimers, producing C → T transitions. This occurs because the SOS mechanism bypasses T∧T dimers promptly, while bypass of cytosine-containing dimers is delayed long enough for deamination to occur. The mutations are thus primarily the product of a faithful mechanism of lesion bypass by a DNA polymerase and are not, as had been generally thought, the product of an error-prone mechanism. All of these observations are explained by the A-rule, which is that adenine nucleotides are inserted noninstructionally opposite DNA lesions.