dGTP starvation in Escherichia coli provides new insights into the thymineless-death phenomenon.
Starvation of cells for the DNA building block dTTP is strikingly lethal (thymineless death, TLD), and this effect is observed in all organisms. The phenomenon, discovered some 60 years ago, is widely used to kill cells in anticancer therapies, but many questions regarding the precise underlying mec...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-05-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1004310 |
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| author | Mark Itsko Roel M Schaaper |
| author_facet | Mark Itsko Roel M Schaaper |
| author_sort | Mark Itsko |
| collection | DOAJ |
| description | Starvation of cells for the DNA building block dTTP is strikingly lethal (thymineless death, TLD), and this effect is observed in all organisms. The phenomenon, discovered some 60 years ago, is widely used to kill cells in anticancer therapies, but many questions regarding the precise underlying mechanisms have remained. Here, we show for the first time that starvation for the DNA precursor dGTP can kill E. coli cells in a manner sharing many features with TLD. dGTP starvation is accomplished by combining up-regulation of a cellular dGTPase with a deficiency of the guanine salvage enzyme guanine-(hypoxanthine)-phosphoribosyltransferase. These cells, when grown in medium without an exogenous purine source like hypoxanthine or adenine, display a specific collapse of the dGTP pool, slow-down of chromosomal replication, the generation of multi-branched nucleoids, induction of the SOS system, and cell death. We conclude that starvation for a single DNA building block is sufficient to bring about cell death. |
| format | Article |
| id | doaj-art-24ead315b44d47d48c8aa948b21bd1c4 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2014-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-24ead315b44d47d48c8aa948b21bd1c42025-08-20T02:22:45ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-05-01105e100431010.1371/journal.pgen.1004310dGTP starvation in Escherichia coli provides new insights into the thymineless-death phenomenon.Mark ItskoRoel M SchaaperStarvation of cells for the DNA building block dTTP is strikingly lethal (thymineless death, TLD), and this effect is observed in all organisms. The phenomenon, discovered some 60 years ago, is widely used to kill cells in anticancer therapies, but many questions regarding the precise underlying mechanisms have remained. Here, we show for the first time that starvation for the DNA precursor dGTP can kill E. coli cells in a manner sharing many features with TLD. dGTP starvation is accomplished by combining up-regulation of a cellular dGTPase with a deficiency of the guanine salvage enzyme guanine-(hypoxanthine)-phosphoribosyltransferase. These cells, when grown in medium without an exogenous purine source like hypoxanthine or adenine, display a specific collapse of the dGTP pool, slow-down of chromosomal replication, the generation of multi-branched nucleoids, induction of the SOS system, and cell death. We conclude that starvation for a single DNA building block is sufficient to bring about cell death.https://doi.org/10.1371/journal.pgen.1004310 |
| spellingShingle | Mark Itsko Roel M Schaaper dGTP starvation in Escherichia coli provides new insights into the thymineless-death phenomenon. PLoS Genetics |
| title | dGTP starvation in Escherichia coli provides new insights into the thymineless-death phenomenon. |
| title_full | dGTP starvation in Escherichia coli provides new insights into the thymineless-death phenomenon. |
| title_fullStr | dGTP starvation in Escherichia coli provides new insights into the thymineless-death phenomenon. |
| title_full_unstemmed | dGTP starvation in Escherichia coli provides new insights into the thymineless-death phenomenon. |
| title_short | dGTP starvation in Escherichia coli provides new insights into the thymineless-death phenomenon. |
| title_sort | dgtp starvation in escherichia coli provides new insights into the thymineless death phenomenon |
| url | https://doi.org/10.1371/journal.pgen.1004310 |
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