Control of ribonucleotide reductase in heat- and cold-sensitive mammalian cell-cycle mutants.
Two heat-sensitive (reversibly arrested in G1 phase at 39.5 degrees C, multiplying at 33 degrees C) and two cold-sensitive (reversibly arrested in G1 phase at 33 degrees C, multiplying at 39.5 degrees C) cell-cycle mutants of the P-815-X2 murine mastocytoma line were tested for ribonucleotide reductase activity, using cells made permeable to nucleotides. After transfer of the heat-sensitive mutant cells to 39.5 degrees C, ribonucleotide reductase activity, similar to thymidine kinase (Schneider, E., Müller, B. and Schindler, R. (1983) Biochim. Biophys. Acta 741, 77-85), but unlike DNA polymerase alpha (Schneider, E., Müller, B. and Schindler, R. (1985) Biochim. Biophys. Acta 825, 375-383), decreased rapidly and in parallel with numbers of cells in S phase, whereas in the cold-sensitive mutant cells brought to 33 degrees C, ribonucleotide reductase activity decreased approx. 8 h later than numbers of DNA-synthesizing cells. When arrested heat- or cold-sensitive mutant cells were returned to the permissive temperature, ribonucleotide reductase activities, similar to DNA polymerase alpha and to thymidine kinase in heat-sensitive mutants, increased essentially in parallel with reentry of cells into S phase, whereas the increase in thymidine kinase activity in the cold-sensitive mutants was previously shown to occur approx. one cell-cycle time later. This indicates that ribonucleotide reductase and thymidine kinase are coordinately expressed in the heat-sensitive, but independently regulated in the cold-sensitive mutants.
Schaer
J C
JC
Department of Pathology, University of Bern, Switzerland.
Maurer
U
U
Schindler
R
R
D000818:Animals; D002453:Cell Cycle; D003080:Cold Temperature; D004247:DNA / Q000096:biosynthesis; D006358:Hot Temperature; D007399:Interphase; D012515:Mast-Cell Sarcoma; D051379:Mice; D009154:Mutation; D012264:Ribonucleotide Reductases / Q000378:metabolism*; D013937:Thymidine Kinase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004247:DNA; D012264:Ribonucleotide Reductases; D013937:Thymidine Kinase