The goal of this proposal is to define the genetic network that coordinates the initiation of DNA replication with cell cycle progression. Caulobacter crescentus is particularly well suited to the identification and analysis of the regulatory factors that mediate replication initiation and chromosome movement in a simple bacterial cell with a well-defined cell cycle. The unique characteristics of Caulobacter include ease of cell synchrony, one and only one replication of the single chromosome per cell cycle, a clear G1, S, and G2 period, and an asymmetric division that yield progeny with distinct morphological features and different cell fates. The initiation of DNA replication is under the negative control of the CtrA response regulator which binds to the replication origin. CtrA is temporally controlled by phosphorylation and proteolysis, and is asymmetrically restricted to the non-replicating progeny swarmer cell. In addition, expression of the genes encoding the replication machinery are induced at the time of replication initiation and coordinately regulated, and a new DNA methylating enzyme, CcrM, contributes to the control of replication initiation, providing yet other layers of regulation. The proposed experiments will seek to coordinate these layers of control with the factors that control cell cycle induction of the genes encoding the replication machinery, determine the role of DNA methylation sites in the replication origin, and define the regulatory mechanisms that confine the CcrM DNA methyltransferase to a specific time period late in the cell cycle. Components of the chromosome segregation apparatus will also be identified and how they are cued to the progression of chromosome replication will be determined.
| Lasker, Keren; Schrader, Jared M; Men, Yifei et al. (2016) CauloBrowser: A systems biology resource for Caulobacter crescentus. Nucleic Acids Res 44:D640-5 |
| Schrader, Jared M; Shapiro, Lucy (2015) Synchronization of Caulobacter crescentus for investigation of the bacterial cell cycle. J Vis Exp : |
| Zhou, Bo; Schrader, Jared M; Kalogeraki, Virginia S et al. (2015) The global regulatory architecture of transcription during the Caulobacter cell cycle. PLoS Genet 11:e1004831 |
| Ptacin, Jerod L; Gahlmann, Andreas; Bowman, Grant R et al. (2014) Bacterial scaffold directs pole-specific centromere segregation. Proc Natl Acad Sci U S A 111:E2046-55 |
| Gonzalez, Diego; Kozdon, Jennifer B; McAdams, Harley H et al. (2014) The functions of DNA methylation by CcrM in Caulobacter crescentus: a global approach. Nucleic Acids Res 42:3720-35 |
| Schrader, Jared M; Zhou, Bo; Li, Gene-Wei et al. (2014) The coding and noncoding architecture of the Caulobacter crescentus genome. PLoS Genet 10:e1004463 |
| Childers, W Seth; Xu, Qingping; Mann, Thomas H et al. (2014) Cell fate regulation governed by a repurposed bacterial histidine kinase. PLoS Biol 12:e1001979 |
| Mera, Paola E; Kalogeraki, Virginia S; Shapiro, Lucy (2014) Replication initiator DnaA binds at the Caulobacter centromere and enables chromosome segregation. Proc Natl Acad Sci U S A 111:16100-5 |
| Kozdon, Jennifer B; Melfi, Michael D; Luong, Khai et al. (2013) Global methylation state at base-pair resolution of the Caulobacter genome throughout the cell cycle. Proc Natl Acad Sci U S A 110:E4658-67 |
| Blair, Jimmy A; Xu, Qingping; Childers, W Seth et al. (2013) Branched signal wiring of an essential bacterial cell-cycle phosphotransfer protein. Structure 21:1590-601 |
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