Evidence that a critical threshold of DNA polymerase-alpha activity may be required for the initiation of DNA synthesis in mammalian cell heterokaryons
| Autor: | George M. Martin, Glenna C. Burmer, Anthony C. Saulewicz, William R. Pendergrass, Peter S. Rabinovitch, Thomas H. Norwood |
|---|---|
| Rok vydání: | 1982 |
| Předmět: |
DNA Replication
Cell type Physiology DNA polymerase Cell Survival Clinical Biochemistry Cell DNA-Directed DNA Polymerase Hybrid Cells Cell Line chemistry.chemical_compound medicine Humans Nucleic Acid Synthesis Inhibitors Heterokaryon biology DNA synthesis Cell Cycle Cell Biology DNA Molecular biology medicine.anatomical_structure Cell Transformation Neoplastic Phenotype chemistry Cell culture biology.protein Specific activity |
| Zdroj: | Journal of cellular physiology. 113(1) |
| ISSN: | 0021-9541 |
| Popis: | The specific activity of DNA polymerase (90% alpha) was determined in nine "neoplastoid" cell lines (Martin and Sprague, 1973) and in three different strains of HDF (human diploid fibroblast-like cells), all examined in logarithmic phases of growth. This was compared to the ability of each cell type to "rescue" (reinitiate DNA synthesis in) senescent HDF cells subsequent to polyethylene glycol-mediated cell fusions. A sharp "threshold" value of DNA polymerase activity was observed below which reinitiation of DNA synthesis in heterokaryons with senescent HDF does not occur. This threshold was especially obvious when the specific activity of DNA polymerase (p moles dTTP incorporated per mg protein or per cell) was divided by the percent of S-phase cells present in each culture as determined by flow microfluorometry. Our results indicate that the specific activity of DNA polymerase-alpha (or some other factor tightly coregulated with it) in "recessive" cell types (those unable to rescue senescent cells) is only about two times this theoretical "threshold" value, and that fusion of recessive cell types to senescent HDF cells reduces the specific activity in the heterokaryon to below this minimum, thus preventing the cells from entering S phase. |
| Databáze: | OpenAIRE |
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