Normal expression of thymidine kinase and O6-methylguanine-DNA methyltransferase in cultured fibroblasts from individuals with hereditary galactokinase deficiency.
Expression of the enzymes galactokinase, thymidine kinase, and O6-methylguanine-DNA methyltransferase is occasionally coordinately regulated in human cell lines. We have measured the activities of these three enzymes in extracts of fibroblasts from individuals with hereditary galactokinase deficiency. These cells do not express measurable galactokinase activity. The levels of O6-methylguanine-DNA methyltransferase were in the normal range in cells from three galactokinase-deficient individuals. The activity of thymidine kinase in the affected cells was in the normal range for two of the three individuals. The reduced thymidine kinase activity in the third individual reflected the extremely poor growth of the cells in culture. Immortalization of one galactokinase-deficient cell line resulted in loss of O6-methylguanine-DNA methyltransferase activity, but the galactokinase and thymidine kinase levels remained unchanged. The data indicate that the loss of galactokinase activity in these individuals is the consequence of an alteration of gene expression which does not involve coordinate silencing with the thymidine kinase and methyltransferase loci.
Stephenson
C
C
Imperial Cancer Research Fund, Clare Hall Laboratories, Hertfordshire, U.K.
Brivet
M
M
Gautier
M
M
Deschatrette
J
J
Gitzelmann
R
R
Karran
P
P
D002460:Cell Line; D002474:Cell-Free System; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000201:enzymology*; D005686:Galactokinase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006720:Homozygote; D006801:Humans; D008780:Methyltransferases / Q000096:biosynthesis / Q000235:genetics*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics*
D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D013937:Thymidine Kinase; D005686:Galactokinase