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14:53
Analysis of Global RNA Synthesis at the Single Cell Level following Hypoxia
Published on: May 14, 2014
Ribonucleotide reductase, a possible agent in deoxyribonucleotide pool asymmetries induced by hypoxia
K Chimploy1, M L Tassotto, C K Mathews
1Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331-7305, USA.
The Journal of Biological Chemistry
|September 28, 2000
Summary
Low oxygen levels expand most deoxyribonucleoside triphosphate (dNTP) pools but deplete dCTP. This study found oxygen limitation specifically affects GDP reduction by ribonucleotide reductase, not CDP reduction.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Respiration
Background:
- Mammalian cells exhibit natural asymmetries in deoxyribonucleoside triphosphate (dNTP) pools.
- Low oxygen atmospheres (2% O2) cause significant dNTP pool expansions (dATP, dGTP, dTTP) and dCTP depletion in V79 hamster lung cells.
- Previous hypotheses suggest oxygen's role in ribonucleotide reductase (RNR) activity underlies these changes.
Purpose of the Study:
- To test if oxygen limitation specifically affects the ribonucleotide specificity of mouse ribonucleotide reductase.
- To investigate the impact of varying oxygen tensions on RNR activity and substrate reduction.
Main Methods:
- Utilized recombinant mouse ribonucleotide reductase.
- Developed an assay for simultaneous monitoring of all four nucleotide substrate reductions.
- Investigated enzyme activity under anaerobic conditions and after hydroxyurea treatment followed by exposure to varying oxygen levels.
Main Results:
- Anaerobic conditions caused only partial loss of enzyme activity.
- Hydroxyurea treatment completely depleted activity, which was largely restored by exposure to air.
- CDP reduction was not specifically sensitive to oxygen depletion, but GDP reduction was specifically sensitive.
Conclusions:
- Oxygen limitation specifically impacts GDP reduction by ribonucleotide reductase, explaining observed dNTP pool alterations.
- The differential oxygen sensitivity does not appear to be due to varying allosteric forms or altered effector responses at low oxygen.
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