Antifolate-induced misincorporation of deoxyuridine monophosphate into DNA by cells from patients with the fragile X syndrome.
The fragile site at Xq27 is expressed in vitro under conditions that lead to decreased intracellular thymidine triphosphate concentration, a condition which has also been shown to promote the misincorporation into DNA of deoxyuridine monophosphate (dUMP) in place of thymidine. We tested for increased whole-cell misincorporation of dUMP as a possible molecular mechanism for the expression of the fragile X abnormality. Neither deoxyuridine triphosphatase nor uracil-DNA-glycosylase, the two enzymes that normally prevent the accumulation of dUMP in DNA, was deficient in fragile X syndrome cells. Misincorporation of dUMP occurred in comparably low levels in both normal and fragile X syndrome lymphoblasts. Although these results provide strong evidence against generalized misincorporation of dUMP in fragile X syndrome cells, a substantial real difference present at Xq27 might not be detected in these studies of whole cells containing the diploid chromosome complement.
Wang
J C
JC
Beardsley
G P
GP
Erbe
R W
RW
D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D045647:DNA Glycosylases; D003856:Deoxyuracil Nucleotides / Q000378:metabolism*; D005467:Floxuridine / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D011739:Pyrimethamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011755:Pyrophosphatases / Q000378:metabolism; D012729:Sex Chromosome Aberrations / Q000235:genetics*; D051981:Uracil-DNA Glycosidase
D003856:Deoxyuracil Nucleotides; D005493:Folic Acid Antagonists; D005467:Floxuridine; C006308:metoprine; D004247:DNA; C007267:2'-deoxyuridylic acid; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase; D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase; D011739:Pyrimethamine