Reading and misreading 8-oxoguanine, a paradigmatic ambiguous nucleobase

Anna V. Yudkina, Evgeniy S. Shilkin, Anton V. Endutkin, Alena V. Makarova, Dmitry O. Zharkov

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

7,8-Dihydro-8-oxoguanine (oxoG) is the most abundant oxidative DNA lesion with dual coding properties. It forms both Watson–Crick (anti)oxoG:(anti)C and Hoogsteen (syn)oxoG:(anti)A base pairs without a significant distortion of a B-DNA helix. DNA polymerases bypass oxoG but the accuracy of nucleotide incorporation opposite the lesion varies depending on the polymerase-specific interactions with the templating oxoG and incoming nucleotides. High-fidelity replicative DNA polymerases read oxoG as a cognate base for A while treating oxoG:C as a mismatch. The mutagenic e_ects of oxoG in the cell are alleviated by specific systems for DNA repair and nucleotide pool sanitization, preventing mutagenesis from both direct DNA oxidation and oxodGMP incorporation. DNA translesion synthesis could provide an additional protective mechanism against oxoG mutagenesis in cells. Several human DNA polymerases of the X- and Y-families e_ciently and accurately incorporate nucleotides opposite oxoG. In this review, we address the mutagenic potential of oxoG in cells and discuss the structural basis for oxoG bypass by di_erent DNA polymerases and the mechanisms of the recognition of oxoG by DNA glycosylases and dNTP hydrolases.

Original languageEnglish
Article number269
Number of pages31
JournalCrystals
Volume9
Issue number5
DOIs
Publication statusPublished - 1 May 2019

Keywords

  • 7,8-Dihydro-8-oxoguanine
  • Base excision repair
  • DNA glycosylases
  • DNA polymerases
  • Mutagenesis
  • Nucleotide hydrolases
  • Translesion DNA synthesis
  • translesion DNA synthesis
  • OXIDATIVELY DAMAGED DNA
  • STEADY-STATE KINETICS
  • ACTIVE-SITE
  • CRYSTAL-STRUCTURE
  • HUMAN DNA-POLYMERASE
  • ESCHERICHIA-COLI
  • base excision repair
  • mutagenesis
  • 8-Dihydro-8-oxoguanine
  • ERROR-PRONE REPLICATION
  • BASE EXCISION-REPAIR
  • COLI MUTY GENE
  • 7
  • nucleotide hydrolases
  • NUDIX HYDROLASE

Fingerprint

Dive into the research topics of 'Reading and misreading 8-oxoguanine, a paradigmatic ambiguous nucleobase'. Together they form a unique fingerprint.

Cite this