Biochemical analysis of H₂O₂-induced mutation spectra revealed that multiple damages were involved in the mutational process.

ABSTRACT: Reactive oxygen species (ROS) are a major threat to genomic integrity and believed to be one of the etiologies of cancers. Here we developed a cell-free system to analyze ROS-induced mutagenesis, in which DNA was exposed to H₂O₂ and then subjected to translesion DNA synthesis by various DNA polymerases. Then, frequencies of mutations on the DNA products were determined by using next-generation sequencing technology. The majority of observed mutations were either C>A or G>A, caused by dAMP insertion at G and C residues, respectively. These mutations showed similar spectra to COSMIC cancer mutational signature 18 and 36, which are proposed to be caused by ROS. The in vitro mutations can be produced by replicative DNA polymerases (yeast DNA polymerase δ and ε), suggestin

SUBMITTER: Sugiyama T 

PROVIDER: S-EPMC10842480 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature