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Survival of DNA Damage in Yeast Directly Depends on Increased dNTP Levels Allowed by Relaxed Feedback Inhibition of Ribonucleotide Reductase
The ribonucleotide reductase inhibitor Sml1 is a new target of the Mec1/Rad53 kinase cascade during growth and in response to DNA damage
It is shown that Sml1 is a new target of the DNA damage checkpoint and its removal is a conserved function of Mec1 and Rad53 during growth and after damage.
Reduction of ribonucleotides.
Structural Aspects and Reaction Mechanism; Regulation of Enzyme Synthesis; and Correlation o f I n Vitro and I n Vivo Activities.
Regulation of Mammalian Ribonucleotide Reduction and dNTP Pools after DNA Damage and in Resting Cells*
- Pelle Håkansson, A. Hofer, L. Thelander
- Biology, ChemistryJournal of Biological Chemistry
- 24 March 2006
The results emphasize the importance of the low constitutive levels of p53R2 in mammalian cells, which together with low levels of R1 protein may be essential for the supply of dNTPs for basal levels of DNA repair and mitochondrial DNA synthesis in Go/G1 cells.
Cell cycle-dependent expression of mammalian ribonucleotide reductase. Differential regulation of the two subunits.
Cid13 Is a Cytoplasmic Poly(A) Polymerase that Regulates Ribonucleotide Reductase mRNA
Yeast Sml1, a Protein Inhibitor of Ribonucleotide Reductase*
- A. Chabes, V. Domkin, L. Thelander
- Biology, ChemistryThe Journal of Biological Chemistry
- 17 December 1999
This work uses highly purified recombinant proteins to directly demonstrate that the Sml1 protein is a strong inhibitor of yeast RNR, and specifically binds to the yeast Rnr1p in a 1:1 ratio with a dissociation constant of 0.4 μm.
Mouse ribonucleotide reductase R2 protein: A new target for anaphase-promoting complex-Cdh1-mediated proteolysis
- A. Chabes, C. Pfleger, M. Kirschner, L. Thelander
- BiologyProceedings of the National Academy of Sciences…
- 24 March 2003
It is demonstrated that the mitotic degradation and hence the overall periodicity of R2 protein levels depends on a KEN box sequence, recognized by the Cdh1–anaphase-promoting complex, recognized during mitosis/G1 in R2protein-overexpressing cells.
Controlled Protein Degradation Regulates Ribonucleotide Reductase Activity in Proliferating Mammalian Cells during the Normal Cell Cycle and in Response to DNA Damage and Replication Blocks*
It is shown that in proliferating mammalian cells, the transcription of the R2 gene, once activated in the beginning of S phase, reaches its maximum 6–7 h later and then declines, and DNA damage and replication blocks neither increase nor prolong the R1 promoter activity in S phase.
Mutational and Structural Analyses of the Ribonucleotide Reductase Inhibitor Sml1 Define Its Rnr1 Interaction Domain Whose Inactivation Allows Suppression of mec1 andrad53 Lethality
Seven mutations were identified that did not affect protein expression levels but relieved mec1 and rad53inviability and disrupted the interaction with yeast Rnr3 and human R1, suggesting a conserved binding mechanism between Sml1 and the large subunit of RNR from different species.