Neil3 and NEIL1 DNA Glycosylases Remove Oxidative Damages from Quadruplex DNA and Exhibit Preferences for Lesions in the Telomeric Sequence Context

Abstract

Background: BER of quadruplex structures and telomere DNA has not been well studied. Results: Neil3 and NEIL1 remove damages from quadruplex DNA and show telomeric sequence context effects. Conclusion: Neil3 and NEIL1 may be involved in repair of damages in quadruplex DNA. Significance: This is the first evidence of glycosylase activity on quadruplex DNA and suggests new roles for these enzymes.

Genetic variants in the DNA repair gene NEIL3 and the risk of myocardial infarction in a nested case–control study. The HUNT Study

“…However, as compared with the other DNA glycosylases, NEIL3 seems to be unique structurally, enzymatically and tissue-specifically [24]. NEIL3 incises hydantoins that are 8-oxoG oxidation products in double and single stranded DNA [25,26] as well as other oxidative base lesions in single-stranded DNA [25,26], telomere sequences and G4 quadruplex structures [27]. In mice, Neil3 is found to be highly expressed in hematopoietic tissue and testis, during embryonic development and in progenitor rich regions in the brain, while human NEIL3 is found to be highly expressed in thymus, testis and in multiple forms of cancer [28][29][30][31][32].…”

Diverse effects of naturally occurring base lesions on the structure and stability of the human telomere DNA quadruplex

“…alkyltransferase [72], and further oxidized products of 8-oxoguanine are also removed by the NEIL glycosylases [37], although 8-oxoguanine is not [37,73]. Repair of other natural lesions forming in telomeric quadruplexes, including abasic sites and exocyclic, both the acyclic and cyclic adducts of bases are not known at present.…”

“…All these modified nucleotides were site-specifically incorporated into the tetrads of the tree-tetrad forming htel oligonucleotide sequences. There are few publications on loop modifications: the thymine glycol replacing thymine [37], 8-oxoA replacing adenine in the TTA loops [41] and the formation of TeT dimers of the same-type of loop [42]. On the other hand, there are a plethora of studies on incorporating nonnatural modified nucleotides into the loops of various quadruplex scaffolds (reviewed in Ref.…”

G-Quadruplex in the NRF2 mRNA 5′ Untranslated Region Regulates De Novo NRF2 Protein Translation under Oxidative Stress

“…8-Oxoguanine in telomeric DNA influences the binding and activity of telomerase (82,83). In addition, 8-oxoguanine enhances the binding of helicase and DNA repair enzymes to telomeric DNA (84,85). This points to the possibility that the oxidation of the NRF2 5=-UTR G-quadruplex facilitates its binding to EF1a.…”