David Sherratt
Bacterial Chromosome Dynamics
Co-workers: Lidia Arciszewska, Anjana Badrinarayanan, Rachel Baker, Estelle Crozat, Jenny Emerson, James Graham, Ian Grainge, Heather Hendrickson, Bing Li, Rodrigo Reyes, Xindan Wang
Our research is aimed at understanding how DNA replication, recombination and chromosome segregation shape bacterial chromosome organization in the context of the living cell. The research observes where genes and molecular machines are positioned as a cell proceeds through its growth and division cycles, and what happens when normal cellular behaviour is perturbed by different methods. Individual components of DNA organizing and processing machines are studied genetically, structurally and biochemically, and information on their molecular action is integrated into the context of their action in cells.
Up to three separate green fluorescent protein fusions to DNA binding proteins, which mark specific genes, and molecular machine components can be simultaneously tracked in living cells, thereby relating the assembly of DNA processing machinery in time and space to gene position within chromosomes. Either DNA replication or chromosome segregation can be impaired and the consequences on DNA processing and cell division visualized. Furthermore, the mechanism of action of the SMC complex, MukBEF, in organizing newly replicated DNA and the action of the FtsK DNA translocase in chromosome segregation are being investigated at the biochemical, structural and cellular levels.
Publications
- Reyes-Lamothe R., Possoz C., Danilova O. and Sherratt D.J. (2008). Independent positioning and action of E. colii replication forks in living cells. Cell 133, 90-102
- Lowe, J., Ellonen, A., Allen, M., Atkinson, C., Sherratt, D. J. and Grainge, I. (2008). Molecular mechanism of sequence-directed DNA loading and translocation by FtsK. Mol. Cell 31, 498-509
- Wang, X., Reyes-Lamothe, R. and Sherratt, D.J. (2008) Modulation of Escherichia coli sister cohesion by topoisomerase IV. Genes. Dev. 22, 2426-2433
- Reyes-Lamothe R., Wang, X. and Sherratt D.J. (2008). Escherichia coli and its chromosome. Trends Microbiol. 16, 238-245
- Massey T.H., Mercogliano C.P., Yates J., Sherratt D.J., Löwe J. (2006). Double-stranded DNA translocation: structure and mechanism of hexaxmeric FtsK. Mol. Cell, 23: 457-469
More Publications...
Research Images
Figure 1: The genetic map of the E.coli chromosome is recapitulated in living cells, with a translational symmetry relating the chromosomes in sisters [4]
Figure 2: Crystal structure of the motor domain of the FtsK translocase [3]
Figure 3: Co-crystal of the FtsK regulatory domain, complexed with KOPS DNA, which can act to load FtsK or to down-regulate its motor activity [5]
Figure 4: 2-D gel analysis of site-specific replication fork stalling and restart, induced by repressor binding to an array of operators and release [4]
Contact:david.sherratt@bioch.ox.ac.uk
Graduate Student and Postdoctoral Positions: Enquiries with CV welcome
Website: http://www2.bioch.ox.ac.uk/sherrattlab