Department of Chemistry, University of Missouri, 125 Chemistry Building, Columbia, Missouri 65211, United States.
Department of Biochemistry, University of Missouri, Columbia, Missouri 65211, United States.
Chem Res Toxicol. 2022 Feb 21;35(2):218-232. doi: 10.1021/acs.chemrestox.1c00409. Epub 2022 Feb 7.
Hydrolytic loss of nucleobases from the deoxyribose backbone of DNA is one of the most common unavoidable types of damage in synthetic and cellular DNA. The reaction generates abasic sites in DNA, and it is important to understand the properties of these lesions. The acidic nature of the α-protons of the ring-opened abasic aldehyde residue facilitates the β-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 -α,β-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. We characterized the strand cleavage induced by the treatment of an abasic site-containing DNA oligonucleotide with heat, NaOH, piperidine, spermine, and the base excision repair glycosylases Fpg and Endo III. The results showed that under multiple conditions, cleavage at an abasic site in a DNA oligomer generated noncanonical sugar remnants including -α,β-unsaturated aldehyde, 2-deoxyribose, and 3-thio-2,3-dideoxyribose products on the 3'-terminus of the strand break.
脱氧核糖核酸（DNA）的核糖骨架上的碱基发生水解丢失是合成和细胞 DNA 中最常见的不可避免的损伤类型之一。该反应会在 DNA 中产生无碱基位点，了解这些损伤的性质非常重要。开环无碱基醛残基的α-质子的酸性性质促进了 3'-磷酸基的β消除。预计该反应将生成带有 5'-末端磷酸基和 3'-末端 -α,β-不饱和醛残基的 DNA 链断裂；然而，少数研究已经在 3'-末端鉴定出非典型的糖残基，这表明 DNA 中无嘌呤/无嘧啶位点的链断裂产生的产物可能比通常认为的更为复杂。我们用热、NaOH、哌啶、亚精胺以及碱基切除修复糖苷酶 Fpg 和 Endo III 处理含无碱基位点的 DNA 寡核苷酸来表征诱导的链断裂。结果表明，在多种条件下，DNA 寡聚物中无碱基位点的断裂会在链断裂的 3'-末端产生非典型的糖残基，包括 -α,β-不饱和醛、2-脱氧核糖和 3-硫代-2,3-二脱氧核糖产物。
