Kuznetsova Alexandra A, Fedorova Olga S, Kuznetsov Nikita A
Institute of Chemical Biology and Fundamental Medicine of SB RAS, Novosibirsk, Russia.
Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia.
Front Cell Dev Biol. 2020 Nov 30;8:595687. doi: 10.3389/fcell.2020.595687. eCollection 2020.
Human telomeres as well as more than 40% of human genes near the promoter regions have been found to contain the sequence that may form a G-quadruplex structure. Other non-canonical DNA structures comprising bulges, hairpins, or bubbles may have a functionally important role during transcription, replication, or recombination. The guanine-rich regions of DNA are hotspots of oxidation that forms 7,8-dihydro-8-oxoguanine, thymine glycol, and abasic sites: the lesions that are handled by the base excision repair pathway. Nonetheless, the features of DNA repair processes in non-canonical DNA structures are still poorly understood. Therefore, in this work, a comparative analysis of the efficiency of the removal of a damaged nucleotide from various G-quadruplexes and bulged structures was performed using endonuclease VIII-like 1 (NEIL1), human 8-oxoguanine-DNA glycosylase (OGG1), endonuclease III (NTH1), and prokaryotic formamidopyrimidine-DNA glycosylase (Fpg), and endonuclease VIII (Nei). All the tested enzymes were able to cleave damage-containing bulged DNA structures, indicating their important role in the repair process when single-stranded DNA and intermediate non-B-form structures such as bubbles and bulges are formed. Nevertheless, our results suggest that the ability to cleave damaged quadruplexes is an intrinsic feature of members of the H2tH structural family, suggesting that these enzymes can participate in the modulation of processes controlled by the formation of quadruplex structures in genomic DNA.
人们发现人类端粒以及启动子区域附近超过40%的人类基因都含有可能形成G-四链体结构的序列。其他非经典DNA结构，包括凸起、发夹或气泡，可能在转录、复制或重组过程中发挥重要的功能作用。DNA富含鸟嘌呤的区域是氧化热点，会形成7,8-二氢-8-氧代鸟嘌呤、胸腺嘧啶乙二醇和无碱基位点：这些损伤由碱基切除修复途径处理。然而，非经典DNA结构中DNA修复过程的特点仍知之甚少。因此，在这项工作中，使用类核酸内切酶VIII样1（NEIL1）、人类8-氧代鸟嘌呤-DNA糖基化酶（OGG1）、核酸内切酶III（NTH1）、原核甲酰胺嘧啶-DNA糖基化酶（Fpg）和核酸内切酶VIII（Nei），对从各种G-四链体和凸起结构中去除受损核苷酸的效率进行了比较分析。所有测试的酶都能够切割含有损伤的凸起DNA结构，表明它们在单链DNA以及气泡和凸起等中间非B型结构形成时的修复过程中发挥重要作用。然而，我们的结果表明，切割受损四链体的能力是H2tH结构家族成员的固有特征，这表明这些酶可以参与调控由基因组DNA中四链体结构形成所控制的过程。
