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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bianchi, V. Pontis, E. Reichard, P. |
| Abstract | Degradation of pyrimidine deoxyribonucleoside triphosphates plays a major role in the regulation of their pool sizes in 3T6 cells. During normal growth, these cells excrete deoxyribonucleosides (mostly deoxyuridine) into the medium. When DNA strand elongation is inhibited, de novo synthesis of dCTP and dTTP continues, followed by degradation of the deoxyribonucleotides. We now demonstrate that inhibition of de novo synthesis with hydroxyurea stops degradation of deoxyribonucleotides. We now demonstrate that inhibition of de novo synthesis with hydroxyurea stops degradation of deoxyribonucleotides and leads to an influx of deoxyuridine from the medium. This effect appears to be caused by a large drop in the size of the intracellular dUMP pool. We propose that substrate cycles, involving phosphorylation of deoxyribonucleosides by kinases and dephosphorylation of deoxyribonucleoside 5'-phosphates by a nucleotidase, participate in the regulation of the size of pyrimidine deoxyribonucleoside triphosphate pools by directing the flow of deoxyribonucleosides across the cell membrane. While kinases are regulated mainly by allosteric effects, the activity of the nucleotidase appears to be regulated by substrate concentration. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 4 |
| Volume Number | 83 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1986-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Deoxycytosine Nucleotides Biosynthesis Fibroblasts Metabolism Thymine Nucleotides Animals Cell Cycle Cell Line DNA Replication Drug Effects Deoxyribonucleosides Deoxyuracil Nucleotides Dipyridamole Pharmacology Hydroxyurea Mice Phosphorylation Thymidine Monophosphate Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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