Effect of the GC content of DNA on the distribution of UVB-induced bipyrimidine photoproducts

Abstract

Solar UV radiation is a major mutagen that damages DNA through the formation of dimeric photoproducts between adjacent thymine and cytosine bases. A major effect of the GC content of the genome is thus anticipated, in particular in prokaryotes where this parameter significantly varies among species. We quantified the formation of UV-induced photolesions within both isolated and cellular DNA of bacteria of different GC content. First, we could unambiguously show the favored formation of cytosine-containing photoproducts with increasing GC content (from 28 to 72%) in isolated DNA. Thymine–thymine cyclobutane dimer was a minor lesion at high GC content. This trend was confirmed by an accurate and quantitative analysis of the photochemical data based on the exact dinucleotide frequencies of the studied genomes. The observation of the effect of the genome composition on the distribution of photoproducts was then confirmed in living cells, using two marine bacteria exhibiting different GC content. Because cytosine-containing photoproducts are highly mutagenic, it may be predicted that species with genomes exhibiting a high GC content are more susceptible to UV-induced mutagenesis.