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A DNA methylation ratchet governs progression through a bacterial cell cycle.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Collier, Justine McAdams, Harley H. Shapiro, Lucy |
| Copyright Year | 2007 |
| Abstract | The Caulobacter cell cycle is driven by a cascade of transient regulators, starting with the expression of DnaA in G(1) and ending with the expression of the essential CcrM DNA methyltransferase at the completion of DNA replication. The timing of DnaA accumulation was found to be regulated by the methylation state of the dnaA promoter, which in turn depends on the chromosomal position of dnaA near the origin of replication and restriction of CcrM synthesis to the end of the cell cycle. The dnaA gene is preferentially transcribed from a fully methylated promoter. DnaA initiates DNA replication and activates the transcription of the next cell-cycle regulator, GcrA. With the passage of the replication fork, the dnaA promoter becomes hemimethylated, and DnaA accumulation drops. GcrA then activates the transcription of the next cell-cycle regulator, CtrA, once the replication fork passes through the ctrA P1 promoter, generating two hemimethylated copies of ctrA. The ctrA gene is preferentially transcribed from a hemimethylated promoter. CtrA then activates the transcription of ccrM, to bring the newly replicated chromosome to the fully methylated state, promoting dnaA transcription and the start of a new cell cycle. We show that the cell-cycle timing of CcrM is critical for Caulobacter fitness. The sequential changes in the chromosomal methylation state serve to couple the progression of DNA replication to cell-cycle events regulated by the master transcriptional regulatory cascade, thus providing a ratchet mechanism for robust cell-cycle control. |
| Starting Page | 293 |
| Ending Page | 305 |
| Page Count | 13 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.pnas.org/content/104/43/17111.full.pdf |
| PubMed reference number | 17942674v1 |
| Volume Number | 104 |
| Issue Number | 43 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Cascade Device Component Caulobacter Cell Cycle Copy (object) DNA Replication Leukemia, B-Cell Methylation Methyltransferase Promotion (action) Replication Origin Transcription, Genetic replication fork |
| Content Type | Text |
| Resource Type | Article |
