Coregulation of the human O6-methylguanine-DNA methyltransferase with two unrelated genes that are closely linked.

The loss of expression of the enzyme O6-methylguanine-DNA methyltransferase (the Mex- phenotype), which often results from cellular transformation, confers hypersensitivity to alkylating agents. We have observed two unrelated examples in which human cell lines have undergone a spontaneous alteration in their Mex phenotype during propagation in vitro. The change was reversible and was not the result of mutation. In both cases a loss of methyltransferase expression was accompanied by a simultaneous loss of expression of two metabolically unrelated enzymes: thymidine kinase and galactokinase. "Reversion" to methyltransferase expression was accompanied by simultaneous reexpression of both kinase activities. A third example of this coordinate gene regulation was seen with the Burkitt's lymphoma cell line Raji which expresses methyltransferase, thymidine kinase, and galactokinase at high levels. A thymidine kinase- Raji cell line derived by bromodeoxyuridine mutagenesis that is also Mex- was found to be galactokinase-. It appears that methyltransferase expression may in some instances be coordinately regulated with the tk and glk loci which are closely linked on human chromosome 17.