Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
Molecules. 2021 Aug 31;26(17):5285. doi: 10.3390/molecules26175285.
Mutation patterns of DNA adducts, such as mutational spectra and signatures, are useful tools for diagnostic and prognostic purposes. Mutational spectra of carcinogens derive from three sources: adduct formation, replication bypass, and repair. Here, we consider the repair aspect of 1,-ethenoadenine (εA) by the 2-oxoglutarate/Fe(II)-dependent AlkB family enzymes. Specifically, we investigated εA repair across 16 possible sequence contexts (5'/3' flanking base to εA varied as G/A/T/C). The results revealed that repair efficiency is altered according to sequence, enzyme, and strand context (ss- versus ds-DNA). The methods can be used to study other aspects of mutational spectra or other pathways of repair.
DNA 加合物的突变模式,如突变谱和特征,是用于诊断和预后目的的有用工具。致癌物的突变谱源自三个来源:加合物形成、复制绕过和修复。在这里,我们考虑了 2-氧戊二酸/Fe(II)依赖性 AlkB 家族酶对 1, - 烯腺嘌呤(εA)的修复方面。具体来说,我们研究了跨越 16 种可能序列背景(εA 前后 5'/3' 碱基变化为 G/A/T/C)的 εA 修复。结果表明,修复效率根据序列、酶和链背景(ss-DNA 与 ds-DNA)而变化。这些方法可用于研究突变谱的其他方面或其他修复途径。