Excess Folic Acid Exposure Increases Uracil Misincorporation into DNA in a Tissue-Specific Manner in a Mouse Model of Reduced Methionine Synthase Expression.

ABSTRACT:

Background

Folate and vitamin B12 (B12) are cofactors in folate-mediated 1-carbon metabolism (FOCM), a metabolic network that supports synthesis of nucleotides (including thymidylate [dTMP]) and methionine. FOCM impairments such as a deficiency or imbalance of cofactors can perturb dTMP synthesis, causing uracil misincorporation into DNA.

Objective

The purpose of this study was to determine how reduced expression of the B12-dependent enzyme methionine synthase (MTR) and excess dietary folic acid interact to affect folate distribution and markers of genome stability in mouse tissues.

Methods

Heterozygous Mtr knockout mice (Mtr^+/-) model the FOCM-specific effects of B12 deficiency. Folate accumulation and vitamer distribution, genomic uracil concentrations, a

SUBMITTER: Heyden KE 

PROVIDER: S-EPMC11600115 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature