FUdR induction of the X chromosome fragile site: evidence for the mechanism of folic acid and thymidine inhibition.
Experiments designed to illuminate the mechanism by which folic acid and thymidine inhibit expression of the Xq28 fragile site in human lymphocytes are described. The fragile site is induced by 5-fluorodeoxyuridine (FUdR), a potent inhibitor of thymidylate synthetase, in the presence of otherwise inhibiting concentrations of folic acid but not in the presence of thymidine. These results indicate that the fragile site is expressed because of depletion of deoxythymidine monophosphate (dTMP) available for DNA synthesis.
D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005260:Female; D005467:Floxuridine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005492:Folic Acid / Q000494:pharmacology*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008214:Lymphocytes / Q000648:ultrastructure; D008297:Male; D012729:Sex Chromosome Aberrations / Q000235:genetics*; D012730:Sex Chromosomes / Q000187:drug effects*; D013936:Thymidine / Q000494:pharmacology*; D013938:Thymidine Monophosphate / Q000378:metabolism; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D014960:X Chromosome / Q000187:drug effects*
D005467:Floxuridine; D013938:Thymidine Monophosphate; D004247:DNA; D005492:Folic Acid; D013940:Thymidylate Synthase; D013936:Thymidine