NEIL3 promoter G-quadruplex with oxidatively modified bases shows magnesium-dependent folding that stalls polymerase bypass.

ABSTRACT: Oxidative stress unleashes reactive species capable of oxidizing 2'-deoxyguanosine (G) nucleotides in G-rich sequences of the genome, such as the potential G-quadruplex forming sequencing (PQS) in the NEIL3 gene promoter. Oxidative modification of G yields 8-oxo-7,8-dihydro-2'-deoxyguanosine (OG) that can be further oxidized to hydantoin products. Herein, OG was synthesized into the NEIL3 PQS that was allowed to fold to a G-quadruplex (G4) in K⁺ ion solutions with varying amounts of Mg²⁺ in the physiological range. The Mg²⁺ dependency in the oxidatively modified NEIL3 G4 to stall a replicative DNA polymerase was evaluated. The polymerase was found to stall at the G4 or OG, as well as continue to full-length extension with dependency on the location of the m

SUBMITTER: Fleming AM 

PROVIDER: S-EPMC10592359 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature