Thymidylate metabolism in fragile X syndrome cells.
The observation that decreased thymidylate supply in vitro induces the expression of the Xq27 chromosome fragile site prompted us to examine cellular thymidylate metabolism. Using a sensitive enzyme assay for deoxyribonucleotide triphosphates, we found that the total cellular thymidine triphosphate pools in cell lines from fragile X patients and carriers do not differ from normal controls under either basal or folate-deficient conditions. This agrees with our earlier observation that the thymidylate synthase enzyme activities in crude cell extracts of five fragile X syndrome lymphoblast lines do not differ from those in normal controls under standard assay conditions. Although a difference in the amount of thymidine triphosphate available at the replication fork for DNA synthesis remains a possibility, our results indicate that a readily demonstrable defect in thymidylate metabolism is not present in fragile X syndrome cells.
D000782:Aneuploidy; D002460:Cell Line; D003854:Deoxyribonucleotides / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005493:Folic Acid Antagonists / Q000494:pharmacology; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D012264:Ribonucleotide Reductases / Q000378:metabolism; D012729:Sex Chromosome Aberrations / Q000378:metabolism*; D013938:Thymidine Monophosphate / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000032:analysis; D013942:Thymine Nucleotides / Q000096:biosynthesis / Q000378:metabolism*
D003854:Deoxyribonucleotides; D005493:Folic Acid Antagonists; D013942:Thymine Nucleotides; D013938:Thymidine Monophosphate; D005492:Folic Acid; D012264:Ribonucleotide Reductases; D013940:Thymidylate Synthase; C024157:thymidine 5'-triphosphate