Novel insights into strand cleavage at an abasic site in DNA
Abstract
Loss of a nucleobases from the deoxyribose backbone of DNA generates Abasic sites in DNA. Abasic sites are the most common unavoidable DNA damage lesion. It is important to understand the properties of Abasic site. The acidic nature of the [alpha]-protons of the ring-opened abasic aldehyde residue facilitates the [beta]-elimination of the 3'-phosphoryl group. This reaction is expected to generate a DNA strand break with a phosphoryl group on the 5'-terminus and a trans-[alpha],[beta]-unsaturated aldehyde residue on the 3'-terminus; however, a handful of studies have identified noncanonical sugar remnants on the 3'-terminus, suggesting that the products arising from strand cleavage at apurinic/apyrimidinic sites in DNA may be more complex than commonly thought. The strand cleavage in DNA at an abasic site induced by the treatment of heat, NaOH, piperidine, spermine, and the base excision repair glycosylases Fpg and Endo III has been characterized. DNA oligomer generated noncanonical sugar remnants including cis-[alpha],[beta]-unsaturated aldehyde, 2-deoxyribose, and 3-thio-2,3-dideoxyribose products on the 3'-terminus of the strand break. Cells contain millimolar concentration of spermine, which can induce strand cleavage at an abasic site in DNA generate very reactive [alpha],[beta]-unsaturated aldehyde iminium ion. Deoxyguanosine Triphosphate (dGTP) can react with the [alpha],[beta]-unsaturated aldehyde iminium ion of the on the 3'-end of the Ap-derive strand cleavage and generates a previously uncharacterized 3'dGTP-ddR adduct.
Degree
Ph. D.