Ribonucleotide reductase (RNR) plays a central role in the formation and control of the optimal levels of deoxyribonucleoside triphosphates, which are required for DNA replication and DNA repair processes. Mammalian RNRs are composed of two nonidentical subunits, proteins R1 and R2. The levels of the limiting R2 protein control overall RNR activity during the cell cycle, being undetectable in G1 phase and increasing in S phase. We show that in proliferating mammalian cells, the transcription of the R2 gene, once activated in the beginning of S phase, reaches its maximum 6-7 hours later and then declines. Interestingly, DNA damage and replication blocks, which arrest the cell cycle, neither increase nor prolong the R2 promoter activity in S phase; consequently, the R2 promoter activity is uncoupled from the S phase progression. Contrary to the existing transcriptional model, we demonstrate that the cell cycle activity of the mammalian RNR is controlled by an S-phase specific stabilization of the R2 protein, which is effective until cells pass into mitosis, when the protein is rapidly degraded.1308 Mimosine induces p27Kipl expression via transcriptional activation
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.