Back to Search
Start Over
The ribonucleotide reductase inhibitor Sml1 is a new target of the Mec1/Rad53 kinase cascade during growth and in response to DNA damage.
- Source :
-
The EMBO journal [EMBO J] 2001 Jul 02; Vol. 20 (13), pp. 3544-53. - Publication Year :
- 2001
-
Abstract
- The evolutionarily conserved protein kinases Mec1 and Rad53 are required for checkpoint response and growth. Here we show that their role in growth is to remove the ribonucleotide reductase inhibitor Sml1 to ensure DNA replication. Sml1 protein levels fluctuate during the cell cycle, being lowest during S phase. The disappearance of Sml1 protein in S phase is due to post-transcriptional regulation and is associated with protein phosphorylation. Both phosphorylation and diminution of Sml1 require MEC1 and RAD53. More over, failure to remove Sml1 in mec1 and rad53 mutants results in incomplete DNA replication, defective mitochondrial DNA propagation, decreased dNTP levels and cell death. Interestingly, similar regulation of Sml1 also occurs after DNA damage. In this case, the regulation requires MEC1 and RAD53, as well as other checkpoint genes. Therefore, 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.
- Subjects :
- Checkpoint Kinase 2
DNA, Fungal drug effects
DNA, Fungal genetics
DNA, Fungal radiation effects
Gamma Rays
Genotype
Hydroxyurea pharmacology
Intracellular Signaling Peptides and Proteins
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae growth & development
Ultraviolet Rays
Cell Cycle Proteins
DNA Damage
DNA Repair drug effects
DNA Repair radiation effects
DNA Replication drug effects
DNA Replication radiation effects
Enzyme Inhibitors
Fungal Proteins metabolism
Protein Kinases metabolism
Protein Serine-Threonine Kinases
Ribonucleotide Reductases antagonists & inhibitors
Saccharomyces cerevisiae physiology
Saccharomyces cerevisiae Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0261-4189
- Volume :
- 20
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 11432841
- Full Text :
- https://doi.org/10.1093/emboj/20.13.3544