Oxidative stress accelerates repeat sequence instability and base substitutions promoting gastrointestinal driver mutations in MSH2 deficient mice.

ABSTRACT:

Background

Loss of DNA mismatch repair (MMR) increases mutagenesis and tumorigenesis. mutS homolog 2 (MSH2), a central component of the MMR pathway, is essential for correcting base-base mismatches and insertion/deletion loops during DNA replication. To investigate how Msh2 deficiency cooperates with oxidative stress to drive mutagenesis and tumorigenesis, we employed an rpsL reporter gene assay using normal tissues before tumor development following treatment with an oxidizing agent.

Results

The background mutation frequency in the small intestines of Msh2^-/- mice was over 20-fold higher than that of wild-type mice. In addition to G > A base substitutions, frequent 1-bp deletions in adenine mononucleotide repeats ((A)n) in the rpsL gene were observed. Potassium b

SUBMITTER: Ohno M 

PROVIDER: S-EPMC12548293 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature