| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print January 24, 2006
Medical Biochemistry and Biophysics, Medical Biochemistry and Biophysics, Umeå 90187
Corresponding Author: pelle.hakanson{at}medchem.umu.se
Ribonucleotide reductase (RNR) provides the cell with a balanced supply of deoxyribonucleoside triphosphates (dNTP) for DNA synthesis. In budding yeast, DNA damage leads to an upregulation of RNR activity and an increase in dNTP pools which are essential for survival. Mammalian cells contain three non-identical subunits of RNR: one homodimeric large subunit, R1, carrying the catalytic site and two variants of the homodimeric small subunit, R2 and the p53-inducible p53R2, each one containing a tyrosyl free radical essential for catalysis. S-phase specific DNA replication is supported by an RNR consisting of the R1 and R2 subunits. In contrast, DNA damage induces expression of the R1 and the p53R2 subunits. We now show that neither logarithmically growing nor Go/G1-synchronized mammalian cells show any major increase in their dNTP pools after DNA damage. However, non-dividing fibroblasts expressing the p53R2 protein, but not the R2 protein, have reduced dNTP levels if exposed to the RNR-specific inhibitor hydroxyurea, strongly indicating that there is ribonucleotide reduction in resting cells. The slow, 4-fold increase in p53R2 protein expression after DNA damage results in a less than 2-fold increase in the dNTP pools in Go/G1 cells, where the pools are about 5% of the size of the pools in S-phase cells. Our 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.
J. Biol. Chem, 10.1074/jbc.M512894200
Submitted on December 2, 2005
Revised on January 23, 2006
Accepted on January 24, 2006
Regulation of mammalian ribonucleotide reduction and dNTP pools after DNA damage and in resting cells
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Sabouri, J. Viberg, D. K. Goyal, E. Johansson, and A. Chabes Evidence for lesion bypass by yeast replicative DNA polymerases during DNA damage Nucleic Acids Res., October 1, 2008; 36(17): 5660 - 5667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Leanza, P. Ferraro, P. Reichard, and V. Bianchi Metabolic Interrelations within Guanine Deoxynucleotide Pools for Mitochondrial and Nuclear DNA Maintenance J. Biol. Chem., June 13, 2008; 283(24): 16437 - 16445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Shadel Expression and Maintenance of Mitochondrial DNA: New Insights into Human Disease Pathology Am. J. Pathol., June 1, 2008; 172(6): 1445 - 1456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Xu, J. L. Page, J. A. Surtees, H. Liu, S. Lagedrost, Y. Lu, R. Bronson, E. Alani, A. Yu. Nikitin, and R. S. Weiss Broad Overexpression of Ribonucleotide Reductase Genes in Mice Specifically Induces Lung Neoplasms Cancer Res., April 15, 2008; 68(8): 2652 - 2660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Vodnala, A. Fijolek, R. Rofougaran, M. Mosimann, P. Maser, and A. Hofer Adenosine Kinase Mediates High Affinity Adenosine Salvage in Trypanosoma brucei J. Biol. Chem., February 29, 2008; 283(9): 5380 - 5388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Rampazzo, S. Fabris, E. Franzolin, K. Crovatto, M. Frangini, and V. Bianchi Mitochondrial Thymidine Kinase and the Enzymatic Network Regulating Thymidine Triphosphate Pools in Cultured Human Cells J. Biol. Chem., November 30, 2007; 282(48): 34758 - 34769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Gunawardena, S. R. Fox, H. Siddiqui, and E. S. Knudsen SWI/SNF Activity Is Required for the Repression of Deoxyribonucleotide Triphosphate Metabolic Enzymes via the Recruitment of mSin3B J. Biol. Chem., July 13, 2007; 282(28): 20116 - 20123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Pontarin, P. Ferraro, P. Hakansson, L. Thelander, P. Reichard, and V. Bianchi p53R2-dependent Ribonucleotide Reduction Provides Deoxyribonucleotides in Quiescent Human Fibroblasts in the Absence of Induced DNA Damage J. Biol. Chem., June 8, 2007; 282(23): 16820 - 16828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Fijolek, A. Hofer, and L. Thelander Expression, Purification, Characterization, and in Vivo Targeting of Trypanosome CTP Synthetase for Treatment of African Sleeping Sickness J. Biol. Chem., April 20, 2007; 282(16): 11858 - 11865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chabes and B. Stillman Constitutively high dNTP concentration inhibits cell cycle progression and the DNA damage checkpoint in yeast Saccharomyces cerevisiae PNAS, January 23, 2007; 104(4): 1183 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ferraro, L. Nicolosi, P. Bernardi, P. Reichard, and V. Bianchi Mitochondrial deoxynucleotide pool sizes in mouse liver and evidence for a transport mechanism for thymidine monophosphate PNAS, December 5, 2006; 103(49): 18586 - 18591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Rofougaran, M. Vodnala, and A. Hofer Enzymatically Active Mammalian Ribonucleotide Reductase Exists Primarily as an {alpha}6beta2 Octamer J. Biol. Chem., September 22, 2006; 281(38): 27705 - 27711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Pontarin, P. Ferraro, M. L. Valentino, M. Hirano, P. Reichard, and V. Bianchi Mitochondrial DNA Depletion and Thymidine Phosphate Pool Dynamics in a Cellular Model of Mitochondrial Neurogastrointestinal Encephalomyopathy J. Biol. Chem., August 11, 2006; 281(32): 22720 - 22728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Mathews DNA precursor metabolism and genomic stability FASEB J, July 1, 2006; 20(9): 1300 - 1314. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
