• E H Rubin and J G Cory.
• Cancer Res. 1986 Dec 1; 46 (12 Pt 1): 6165-8.

AbstractRibonucleotide reductase catalyzes the rate-limiting step in the de novo synthesis of 2'-deoxyribonucleoside 5'-triphosphates that is required for DNA replication. The mammalian enzyme consists of two nonidentical protein subunits that are both required for enzyme activity. In leukemia L1210 cells, enriched in G1-phase cells by centrifugal elutriation, it was found that ribonucleotide reductase activity increased as the cells progressed to S-phase. The two subunits making up the holoenzyme did not increase coordinately. The nonheme iron subunit increased much more rapidly than the effector-binding (EB) subunit. The activity of the holoenzyme paralleled the level of the EB subunit, which was limiting. The half-lives of the holoenzyme and its subunits were determined in S-phase cells by treatment with cycloheximide. The half-lives of the holoenzyme and the nonheme iron and EB subunits, as determined by enzyme activity, were 3.5, 7.6, and 4 h, respectively. These half-lives are consistent with the data that indicate that the EB subunit is the limiting component in L1210 cells.

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