Nucleic Acids Research Lab, Department of Chemistry, University of Delhi (North Campus), Delhi 110007, India.
Department of Chemistry, Ramjas College, University of Delhi, Delhi 110007, India.
Int J Mol Sci. 2019 Aug 30;20(17):4258. doi: 10.3390/ijms20174258.
Over the decades, oxidative stress has emerged as a major concern to biological researchers. It is involved in the pathogenesis of various lifestyle-related diseases such as hypertension, diabetes, atherosclerosis, and neurodegenerative diseases. The connection between oxidative stress and telomere shortening via oxidative guanine lesion is well documented. Telomeres are confined to guanine rich ends of chromosomes. Owing to its self-association properties, it adopts G-quadruplex structures and hampers the overexpression of telomerase in the cancer cells. Guanine, being the most oxidation prone nucleobase, when structured in G-quadruplex entity, is found to respond peculiarly towards oxidative stress. Interestingly, this non-Watson-Crick structural feature exists abundantly in promoters of various oncogenes, exons and other genomic locations. The involvement of G-quadruplex architecture in oncogene promoters is well recognized in gene regulation processes. Development of small molecules aimed to target G-quadruplex structures, have found to alter the overexpression of oncogenes. The interaction may lead to the obstruction of diseased cell having elevated level of reactive oxygen species (ROS). Thus, presence of short guanine tracts (Gn) forming G-quadruplexes suggests its critical role in oxidative genome damage. Present review is a modest attempt to gain insight on the association of oxidative stress and G-quadruplexes, in various biological processes.
几十年来，氧化应激已成为生物研究人员关注的主要问题。它与各种与生活方式相关的疾病的发病机制有关，如高血压、糖尿病、动脉粥样硬化和神经退行性疾病。氧化应激通过氧化鸟嘌呤损伤与端粒缩短之间的联系已有充分的记录。端粒局限于染色体的富含鸟嘌呤的末端。由于其自缔合特性，它采用 G-四链体结构，并阻碍癌细胞中端粒酶的过度表达。鸟嘌呤是最易氧化的核碱基，当它形成 G-四链体实体时，对氧化应激的反应特别。有趣的是，这种非沃森-克里克结构特征在各种致癌基因、外显子和其他基因组位置的启动子中大量存在。G-四链体结构在癌基因启动子中的参与在基因调控过程中得到了很好的认识。旨在靶向 G-四链体结构的小分子的开发已被发现可以改变致癌基因的过度表达。这种相互作用可能导致病变细胞中活性氧（ROS）水平升高的受阻。因此，短鸟嘌呤（Gn）序列形成 G-四链体的存在表明其在氧化基因组损伤中具有关键作用。本综述是对氧化应激与 G-四链体在各种生物学过程中的关联进行深入了解的一次适度尝试。
