Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA
Bacteria can arrest their own growth and proliferation upon nutrient depletion and under various stressful conditions to ensure their survival. However, the molecular mechanisms responsible for suppressing growth and arresting the cell cycle under such conditions remain incompletely understood. Here...
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2015
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| Online Access: | http://hdl.handle.net/1721.1/98121 https://orcid.org/0000-0002-8288-7607 |
| _version_ | 1826188469012004864 |
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| author | Leslie, David J. Heinen, Christian Schramm, Frederic D. Aakre, Christopher David Murray, Sean M. Laub, Michael T. Jonas, Kristina Thuring, Marietta |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Leslie, David J. Heinen, Christian Schramm, Frederic D. Aakre, Christopher David Murray, Sean M. Laub, Michael T. Jonas, Kristina Thuring, Marietta |
| author_sort | Leslie, David J. |
| collection | MIT |
| description | Bacteria can arrest their own growth and proliferation upon nutrient depletion and under various stressful conditions to ensure their survival. However, the molecular mechanisms responsible for suppressing growth and arresting the cell cycle under such conditions remain incompletely understood. Here, we identify post-transcriptional mechanisms that help enforce a cell-cycle arrest in Caulobacter crescentus following nutrient limitation and during entry into stationary phase by limiting the accumulation of DnaA, the conserved replication initiator protein. DnaA is rapidly degraded by the Lon protease following nutrient limitation. However, the rate of DnaA degradation is not significantly altered by changes in nutrient availability. Instead, we demonstrate that decreased nutrient availability downregulates dnaA translation by a mechanism involving the 5' untranslated leader region of the dnaA transcript; Lon-dependent proteolysis of DnaA then outpaces synthesis, leading to the elimination of DnaA and the arrest of DNA replication. Our results demonstrate how regulated translation and constitutive degradation provide cells a means of precisely and rapidly modulating the concentration of key regulatory proteins in response to environmental inputs. |
| first_indexed | 2024-09-23T08:00:07Z |
| format | Article |
| id | mit-1721.1/98121 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:00:07Z |
| publishDate | 2015 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/981212022-09-30T01:35:13Z Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA Leslie, David J. Heinen, Christian Schramm, Frederic D. Aakre, Christopher David Murray, Sean M. Laub, Michael T. Jonas, Kristina Thuring, Marietta Massachusetts Institute of Technology. Department of Biology Aakre, Christopher David Laub, Michael T. Bacteria can arrest their own growth and proliferation upon nutrient depletion and under various stressful conditions to ensure their survival. However, the molecular mechanisms responsible for suppressing growth and arresting the cell cycle under such conditions remain incompletely understood. Here, we identify post-transcriptional mechanisms that help enforce a cell-cycle arrest in Caulobacter crescentus following nutrient limitation and during entry into stationary phase by limiting the accumulation of DnaA, the conserved replication initiator protein. DnaA is rapidly degraded by the Lon protease following nutrient limitation. However, the rate of DnaA degradation is not significantly altered by changes in nutrient availability. Instead, we demonstrate that decreased nutrient availability downregulates dnaA translation by a mechanism involving the 5' untranslated leader region of the dnaA transcript; Lon-dependent proteolysis of DnaA then outpaces synthesis, leading to the elimination of DnaA and the arrest of DNA replication. Our results demonstrate how regulated translation and constitutive degradation provide cells a means of precisely and rapidly modulating the concentration of key regulatory proteins in response to environmental inputs. National Institutes of Health (U.S.) (Grant 5R01GM082899) 2015-08-20T17:05:53Z 2015-08-20T17:05:53Z 2015-07 2015-03 Article http://purl.org/eprint/type/JournalArticle 1553-7404 1553-7390 http://hdl.handle.net/1721.1/98121 Leslie, David J., Christian Heinen, Frederic D. Schramm, Marietta Thüring, Christopher D. Aakre, Sean M. Murray, Michael T. Laub, and Kristina Jonas. “Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA.” Edited by William F. Burkholder. PLOS Genetics 11, no. 7 (July 2, 2015): e1005342. https://orcid.org/0000-0002-8288-7607 en_US http://dx.doi.org/10.1371/journal.pgen.1005342 PLOS Genetics Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science Public Library of Science |
| spellingShingle | Leslie, David J. Heinen, Christian Schramm, Frederic D. Aakre, Christopher David Murray, Sean M. Laub, Michael T. Jonas, Kristina Thuring, Marietta Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA |
| title | Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA |
| title_full | Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA |
| title_fullStr | Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA |
| title_full_unstemmed | Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA |
| title_short | Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA |
| title_sort | nutritional control of dna replication initiation through the proteolysis and regulated translation of dnaa |
| url | http://hdl.handle.net/1721.1/98121 https://orcid.org/0000-0002-8288-7607 |
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