Folate rescues vitamin B₁₂ depletion-induced inhibition of nuclear thymidylate biosynthesis and genome instability.

ABSTRACT: Clinical vitamin B₁₂ deficiency can result in megaloblastic anemia, which results from the inhibition of DNA synthesis by trapping folate cofactors in the form of 5-methyltetrahydrofolate (5-methylTHF) and subsequent inhibition of de novo thymidylate (dTMP) biosynthesis. In the cytosol, vitamin B₁₂ functions in the remethylation of homocysteine to methionine, which regenerates THF from 5-methylTHF. In the nucleus, THF is required for de novo dTMP biosynthesis, but it is not understood how 5-methylTHF accumulation in the cytosol impairs nuclear dTMP biosynthesis. The impact of vitamin B₁₂ depletion on nuclear de novo dTMP biosynthesis was investigated in methionine synthase-null human fibroblast and nitrous oxide-treated HeLa cell models. The nucleus was the

SUBMITTER: Palmer AM 

PROVIDER: S-EPMC5441772 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature