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

Author:

Ferino Annalisa,Xodo Luigi E.ORCID

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.

Funder

Associazione Italiana per la Ricerca sul Cancro

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Cited by 4 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Oxidative DNA damage on the VEGF G‐quadruplex forming promoter is repaired via long‐patch BER;Environmental and Molecular Mutagenesis;2023-09-05

2. Roles for the 8-Oxoguanine DNA Repair System in Protecting Telomeres From Oxidative Stress;Frontiers in Cell and Developmental Biology;2021-11-19

3. The base excision repair process: comparison between higher and lower eukaryotes;Cellular and Molecular Life Sciences;2021-11-03

4. G-quadruplex DNA: a novel target for drug design;Cellular and Molecular Life Sciences;2021-08-30

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