Human and bacterial DNA polymerases discriminate against 8-oxo-2'-deoxyadenosine-5'-triphosphate

Abstract

Aim. 8-Oxoadenine is an abundant DNA lesion associated with cancer and neurodegeneration. It may appear through direct oxidation of adenine in DNA or by incorporation from the oxidized dNTP pool. Methods. We developed an efficient method of synthesizing 8-oxo-2'-deoxyadenosine-5'-triphosphate and studied its incorporation by various DNA polymerases. Results. oA was weakly misincorporated opposite guanine by the DNA poly-merase I Klenow fragment. Limited incorporation of oA was observed opposite guanine and adenine with DNA polymerase α, and opposite adenine, thymine and guanine with DNA polymerase β. Conclusions. Adenine oxidation in DNA may outweigh damage to dATP as a source of genomic oA.