Effect of DNA Glycosylases OGG1 and Neil1 on Oxidized G-Rich Motif in the KRAS Promoter

Ferino, Annalisa; Xodo, Luigi E.

doi:10.3390/ijms22031137

Open AccessArticle

Effect of DNA Glycosylases OGG1 and Neil1 on Oxidized G-Rich Motif in the KRAS Promoter

by

Annalisa Ferino

and

Luigi E. Xodo

^*

Laboratory of Biochemistry, Department of Medicine, P.le Kolbe 4, 33100 Udine, Italy

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2021, 22(3), 1137; https://doi.org/10.3390/ijms22031137

Submission received: 4 January 2021 / Revised: 19 January 2021 / Accepted: 21 January 2021 / Published: 24 January 2021

(This article belongs to the Special Issue The Polymorphic World of G-Quadruplexes: From Structural Insights to Functional Activity-2nd Edition)

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Abstract

The promoter of the Kirsten ras (KRAS) proto-oncogene contains, upstream of the transcription start site, a quadruplex-forming motif called 32R with regulatory functions. As guanine under oxidative stress can be oxidized to 8-oxoguanine (8OG), we investigated the capacity of glycosylases 8-oxoguanine glycosylase (OGG1) and endonuclease VIII-like 1 (Neil1) to excise 8OG from 32R, either in duplex or G-quadruplex (G4) conformation. We found that OGG1 efficiently excised 8OG from oxidized 32R in duplex but not in G4 conformation. By contrast, glycosylase Neil1 showed more activity on the G4 than the duplex conformation. We also found that the excising activity of Neil1 on folded 32R depended on G4 topology. Our data suggest that Neil1, besides being involved in base excision repair pathway (BER), could play a role on KRAS transcription.

Keywords: G4 DNA; OGG1; Neil1; 8-oxoguanine; KRAS

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MDPI and ACS Style

Ferino, A.; Xodo, L.E. Effect of DNA Glycosylases OGG1 and Neil1 on Oxidized G-Rich Motif in the KRAS Promoter. Int. J. Mol. Sci. 2021, 22, 1137. https://doi.org/10.3390/ijms22031137

AMA Style

Ferino A, Xodo LE. Effect of DNA Glycosylases OGG1 and Neil1 on Oxidized G-Rich Motif in the KRAS Promoter. International Journal of Molecular Sciences. 2021; 22(3):1137. https://doi.org/10.3390/ijms22031137

Chicago/Turabian Style

Ferino, Annalisa, and Luigi E. Xodo. 2021. "Effect of DNA Glycosylases OGG1 and Neil1 on Oxidized G-Rich Motif in the KRAS Promoter" International Journal of Molecular Sciences 22, no. 3: 1137. https://doi.org/10.3390/ijms22031137

APA Style

Ferino, A., & Xodo, L. E. (2021). Effect of DNA Glycosylases OGG1 and Neil1 on Oxidized G-Rich Motif in the KRAS Promoter. International Journal of Molecular Sciences, 22(3), 1137. https://doi.org/10.3390/ijms22031137

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Effect of DNA Glycosylases OGG1 and Neil1 on Oxidized G-Rich Motif in the KRAS Promoter

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