DNA photoreacts by nucleobase ring cleavage to form labile isocyanates

Abstract

Differential infrared absorption spectroscopy was used to study the formation of isocyanates and further photo-products in the oligonucleotides dG₁₀, dC₁₀ and dT₁₀ and in their mononucleosides by ultraviolet light at 266 nm. We find that α-cleavage takes place in oligonucleotides and mononucleosides both in films and in solution. The very intense and spectrally isolated isocyanate (NCO) asymmetric stretch vibration at 2277 cm⁻¹ is used as a spectroscopic marker for detection of the photo-product. The band disappears upon reaction with small amounts of water vapour as expected for isocyanates. Quantum yields for isocyanate formation by nucleobase ring cleavage in the α-position to the carbonyl group are ∼5 × 10⁻⁵ in the mononucleosides and up to 5 × 10⁻⁴ in the oligonucleotides. In the mixed oligonucleotides dG₁₀/dC₁₀ and dA₁₀/dT₁₀ the quantum yield of α-cleavage drops by a factor of 10 compared to the single oligonucleotides. Implications for DNA repair and photo-induced DNA–protein cross-linking via isocyanate reaction with NH₂ groups of amino acids are discussed.