Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulation of the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) has been investigated in a number of human lymphoblastoid cell lines. In a number of Mex- cell lines that do not express methyltransferase activity, CpG sequences in the mgmt gene were hypomethylated with respect to methyltransferase-expressing Mex+ lines. In the cell line GM1953(S), in which the mgmt gene is coregulated with the thymidine kinase and galactokinase genes, reexpression of all three activities was experimentally induced. In this case, the mgmt gene in the nonexpressing cells was found to be hypermethylated and underwent a demethylation at CpG sequences that was coincident with the reappearance of the mgmt mRNA and the three enzyme activities. The simultaneous silencing of three activities in these cells was correlated with an increase in DNA 5-methylcytosine that was widespread throughout the genome. The data indicate that MGMT expression can be controlled epigenetically in human lymphoid cell lines, although the relationship between cytosine methylation and MGMT expression is complex. Furthermore, the rapid alterations in methylation in GM1953(S) cells indicate the existence of signals that can induce widespread and abrupt alterations in cytosine methylation in human cells in culture.
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PMID:Epigenetic silencing of the DNA repair enzyme O6-methylguanine-DNA methyltransferase in Mex- human cells. 139 30

Non-specific generation of intracellular free radicals in excess of normal levels, e.g. by the acute radiation absorption event in cells, has led to a delayed and temporary inhibition of thymidine kinase. The enzyme activity reaches a minimum at 4 h even after a low-level exposure with full recovery soon thereafter. This process appears to represent a biochemical response to an initial physical event, but must be distinguished from the response of the DNA repair enzyme system. A reduction of cellular thymidine kinase activity is expected to cause a temporary reduction of DNA synthesis and may be of advantage to the cell. Such a response may be regarded as an instance of radiation hormesis in the sense that such a compensatory response to the stimulus of irradiation may confer protection against a repeated increase in free radical concentration whether by renewed radiation exposure or by metabolism in general. An improvement of the efficiency of repair or an increased level of free radical detoxification should be of benefit to both the individual cell and to the organism as a whole.
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PMID:Intracellular stimulation of biochemical control mechanisms by low-dose, low-LET irradiation. 357 Aug 5