Human NEIL1 blocking peptide

G-quadruplex is a four-stranded G-rich DNA structure that is highly susceptible to oxidation. Despite the important roles that G-quadruplexes play in telomere biology and gene transcription, neither the impact of guanine lesions on the stability of quadruplexes nor their repair are well understood. Here, we show that the oxidized guanine lesions 8-oxo-7,8-dihydroguanine (8-oxoG), guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp) reduce the thermostability and alter the folding of telomeric quadruplexes in a location-dependent manner. Also, the NEIL1 and NEIL3 DNA glycosylases can remove hydantoin lesions but none of the glycosylases, including OGG1, are able to remove 8-oxoG from telomeric quadruplexes. Interestingly, a hydantoin lesion at the site most prone to oxidation in quadruplex DNA is not efficiently removed by NEIL1 or NEIL3. However, NEIL1, NEIL2 and NEIL3 remove hydantoins from telomeric quadruplexes formed by five TTAGGG repeats much more rapidly than the commonly studied four-repeat quadruplex structures. We also show that APE1 cleaves furan in selected positions in Na+-coordinated telomeric quadruplexes. In promoter G-quadruplex DNA, the NEIL glycosylases primarily remove Gh from Na+-coordinated antiparallel quadruplexes but not K+-coordinated parallel quadruplexes containing VEGF or c-MYC promoter sequences. Thus, the NEIL DNA glycosylases may be involved in both telomere maintenance and in gene regulation.

In spite of the fact that an indirect relationship between NEIL1 gene and Type 2 diabetes has been demonstrated in animal model studies, there have been no human studies showing this relationship. In our study, we aimed to show the relationship between NEIL1 mutation and Type 2 diabetes in humans. The study group consisted 70 patients with Type 2 diabetes and the control group consisted of 50 healthy individuals. The mean age was 53 +/- 11 yr and 49 +/- 11 yr. respectively. Two NEIL1 mutations (2.9%) were detected in the patient group. There was A -> G change (133A -> G) at the 133. position of the 8th exon with 257 bp length in base sequencing. There was no mutation in the control group. We searched NEIL1 gene mutation for the first time in patients with Type 2 diabetes. This mutation was "silent" as it did not cause any amino acid change. The effects of these mutations on the etiopathogenesis of disease are not known. Although the lysine encoded by AAG was identical to the lysine encoded by AAA, it is not dear if they have functional differences due to the changing environmental conditions. NEIL1 gene mutation may have causative role in the development of Type 2 diabetes. (J. Endocrinol. Invest. 35: 401-406, 2012) (C) 2012, Editrice Kurtis