摘要
Most DNA damage caused by oxidative metabolism consists of single lesions that can accumulate in tissues. This review focuses on two classes of lesions: the two 8-oxopurine (8-oxo-Pu) lesions that are repaired by the base excision repair (BER) enzyme and the four 5′,8-cyclopurine (cPu) lesions that are repaired exclusively by the nucleotide excision repair (NER) enzyme. The aim is to correlate the simultaneous quantification of these two classes of lesions in the context of neurological disorders. The first half is a summary of reactive oxygen species (ROS) with particular attention to the pathways of hydroxyl radical (HO•) formation, followed by a summary of protocols for the quantification of six lesions and the biomimetic chemistry of the HO• radical with double-stranded oligonucleotides (ds-ODN) and calf thymus DNA (ct-DNA). The second half addresses two neurodegenerative diseases: xeroderma pigmentosum (XP) and Cockayne syndrome (CS). The quantitative data on the six lesions obtained from genomic and/or mitochondrial DNA extracts across several XP and CS cell lines are discussed. Oxidative stress contributes to oxidative DNA damage by resulting in the accumulation of cPu and 8-oxo-Pu in DNA. The formation of cPu is the postulated culprit inducing neurological symptoms associated with XP and CS.
摘要译文
氧化代谢引起的大多数DNA损伤由可以在组织中积累的单个病变组成。这篇综述着重于两类病变：通过碱基切除修复（BER）酶和四个5'，8-胞肽（CPU）病变修复的两个8-氧嘌呤（8-氧基-PU）病变，这些病变由核苷酸eCection Repair（NER）Enzyme独家修复。目的是将在神经系统疾病的背景下同时量化这两类病变。上半年是活性氧（ROS）的摘要，特别关注羟基自由基（HO•）形成途径，然后是对六个病变进行定量的方案摘要，以及HO•自由基的生物模拟化学与双链寡核苷酸（DS-ds-odn）（DS-ds-odn）和Calf thymus dna（ctymus dna）（ct-dna）（ct-dna）（ct-dna）。下半年解决了两种神经退行性疾病：Xeroderma色素（XP）和Cockayne综合征（CS）。讨论了从几个XP和CS细胞系中基因组和/或线粒体DNA提取物获得的六个病变的定量数据。氧化应激通过导致CPU和8-氧-PU在DNA中的积累而导致氧化DNA损伤。CPU的形成是造成与XP和CS相关的神经系统症状的假定罪魁祸首。
Chryssostomos Chatgilialoglu. Biological Models of Oxidative Purine DNA Damage in Neurodegenerative Disorders[J]. Antioxidants, 2025,14(5): 578