Delaying S-phase progression rescues cells from heat-induced S-phase hypertoxicity
| Autor: | Robert P. Vanderwaal, Michael J. Borrelli, J. L. Roti Roti, Cara L. Griffith, William D. Wright |
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| Rok vydání: | 2001 |
| Předmět: |
Aphidicolin
DNA Replication Saccharomyces cerevisiae Proteins Physiology Cell Survival Clinical Biochemistry Cyclin A Biology S Phase Fungal Proteins chemistry.chemical_compound Heat shock protein Proliferating Cell Nuclear Antigen Replication Protein A Humans Nuclear protein Enzyme Inhibitors Cell Nucleus Endodeoxyribonucleases DNA replication Cell Biology Nuclear matrix Molecular biology Proliferating cell nuclear antigen Cell biology DNA-Binding Proteins Cell killing Exodeoxyribonucleases chemistry biology.protein Cell Division Heat-Shock Response HeLa Cells |
| Zdroj: | Journal of cellular physiology. 187(2) |
| ISSN: | 0021-9541 |
| Popis: | The mechanism by which a cell protects itself from the lethal effects of heat shock and other stress-inducing agents is the subject of much research. We have investigated the relationship between heat-induced damage to DNA replication machinery and the lethal effects of heat shock, in S-phase cells, which are more sensitive to heat shock than either G1 or G2. We found that maintaining cells in aphidicolin, which prevents the passage of cells through S-phase, can rescue S-phase HeLa cells from the lethal effects of heat shock. When S-phase, HeLa cells were held for 5–6 h in 3 μM aphidicolin the measured clonogenic survival was similar to that for exponentially growing cells. It is known, that heat shock induces denaturation or unfolding of proteins, rendering them less soluble and more likely to co-isolate with the nuclear matrix. Here, we show that enhanced binding of proteins involved in DNA replication (PCNA, RPA, and cyclin A), with the nuclear matrix, correlates with lethality of S-phase cells following heat shock under four different experimental conditions. Specifically, the amounts of RPA, PCNA, and cyclin A associated with the nuclear matrix when cells resumed progression through S-phase correlated with cell killing. Heat-induced enhanced binding of nuclear proteins involved with other aspects of DNA metabolism, (Mrell, PDI), do not show this correlation. These results support the hypothesis that heat-induced changes in the binding of proteins associated with DNA replication factories are the potentially lethal lesions, which become fixed to lethal lesions by S-phase progression but are repairable if S-phase progression is delayed. © 2001 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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