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dGTP Starvation in Provides New Insights into the Thymineless-Death Phenomenon


Starvation of cells for DNA precursor dTTP is strikingly lethal in many organisms, like bacteria, yeast, and human cells. This type of death is unusual in that starvation for other nutritional requirements generally results in growth arrest, but not in death. The phenomenon is called thymineless death (TLD), because it was first observed some 60 years ago when a thymine-requiring (thyA) E. coli strain was exposed to growth medium lacking thymine. The TLD phenomenon is of significant interest as it is the basis for several chemotherapeutic (anticancer) treatments in which rapidly growing cells are selectively killed by depletion of the cellular dTTP pool. The precise mechanisms by which cells succumb to dTTP depletion are of significant interest, but have remained elusive for a long time. In the present work, we demonstrate for the first time that the effect is not specific for dTTP starvation. We show that an E. coli strain starved for the DNA precursor dGTP dies in a manner similar to dTTP-starved cells. The effect, which we have termed dGTP starvation, might be exploited - like TLD - therapeutically.


Vyšlo v časopise: dGTP Starvation in Provides New Insights into the Thymineless-Death Phenomenon. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004310
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004310

Souhrn

Starvation of cells for DNA precursor dTTP is strikingly lethal in many organisms, like bacteria, yeast, and human cells. This type of death is unusual in that starvation for other nutritional requirements generally results in growth arrest, but not in death. The phenomenon is called thymineless death (TLD), because it was first observed some 60 years ago when a thymine-requiring (thyA) E. coli strain was exposed to growth medium lacking thymine. The TLD phenomenon is of significant interest as it is the basis for several chemotherapeutic (anticancer) treatments in which rapidly growing cells are selectively killed by depletion of the cellular dTTP pool. The precise mechanisms by which cells succumb to dTTP depletion are of significant interest, but have remained elusive for a long time. In the present work, we demonstrate for the first time that the effect is not specific for dTTP starvation. We show that an E. coli strain starved for the DNA precursor dGTP dies in a manner similar to dTTP-starved cells. The effect, which we have termed dGTP starvation, might be exploited - like TLD - therapeutically.


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