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Effects of Deoxycytidine and Thymidine Kinase Deficiency on Substrate Cycles between Deoxyribonucleosides and Their 5'-Phosphates¹

Department of Biochemistry, Medical Nobel Institute, Karolinska Institutet, S-104 01 Stockholm, Sweden

Substrate cycles constructed from a deoxyribonucleoside kinase and a deoxyribonucleotidase contribute to the metabolism of deoxyribonucleotides in cultured cells. The two enzymes catalyze in opposite directions the irreversible interconversion between a deoxyribonucleoside and its 5'-phosphate. Depending on the balance between the two reactions the net result of the cycle's activity will be synthesis or degradation of the deoxyribonucleotide, and favor import or export of the deoxyribonucleoside. With genetically changed hamster cells (V79 and CHO) deficient in either deoxycytidine or thymidine kinase we now quantify by kinetic isotope flow experiments the contributions of the two kinases to the function of the respective cycles. For each, loss of the relevant kinase was accompanied by an increased degradation of the deoxynucleotide, a slower rate of DNA synthesis, and a longer generation time for the mutant cells. The size of the corresponding deoxyribonucleoside triphosphate pool was apparently not decreased.

¹ This work was supported by grants from the Swedish Medical Research Council and the Medical Faculty of Karolinska Institute.

² To whom requests for reprints should be addressed, at Department of Biochemistry, Medical Nobel Institute, Karolinska Institutet, P. O. Box 60400, S-104 01 Stockholm, Sweden.

Received 11/10/87. Revised 3/ 7/88. Accepted 3/31/88.

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