Research in the Sherratt group 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.
Model of FtsK C-terminal domain with hexameric motor (blue) and trimeric gamma-subdomain (yellow) bound to KOPS (red).
Research
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Chromosome dynamics - tracking genetic loci in space and time
Gene position can be followed in space and time in living cells. Genetic loci are tracked by simultaneous binding of fluorescent repressors to the arrays of their cognate operators inserted into the chromosome regions of interest. Chromosome organization and segregation are also studied in relation to E. coli SMC proteins MukBEF and divisome components, such as FtsZ and FtsK.
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Replisome dynamics - DNA replication, block and restart
The dynamics of the replication machinery (replisome) is studied by labeling replisome components with fluorescent proteins at the normal chromosome locus. Replisome dynamics is also studied in relation to chromosome segregation and cell division. Fluorescent repressor-operator arrays are also used to study reversible replication fork blockage and restart at a specific locus.
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Site-specific recombination and DNA translocase FtsK
FtsK belongs to a family of DNA translocases involved in the acquisition of foreign genes during conjugation and in segregation of chromosomes during spore formation and cell division. In E. coli, FtsK acts at the last stage of chromosome segregation and controls the resolution of chromosome dimers. This latter activity is achieved in combination with site-specific recombinases XerCD acting at dif.
Publications
Our most recent publications...
(PubMed listing):
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Wang X, Lesterlin C, Reyes-Lamothe R, Ball G, Sherratt DJ. (2011)
Replication and segregation of an Escherichia coli chromosome with two replication origins.
Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):E243-50.
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Grainge I, Lesterlin C, Sherratt DJ. (2011)
Activation of XerCD-dif recombination by the FtsK DNA translocase.
Nucleic Acids Res. 2011 Jul;39(12):5140-8.
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Graham JE, Sherratt DJ, Szczelkun MD. (2010)
Sequence-specific assembly of FtsK hexamers establishes directional translocation on DNA.
Proc Natl Acad Sci U S A. 2010 Nov 23; 107(47): 20263-8.
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Wang X, Sherratt DJ. (2010)
Independent segregation of the two arms of the Esherichia coli ori region requires neither RNA synthesis nore MreB dynamics.
J. Bacteriol. 2010 Dec;192(23):6143-53.
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Reyes-Lamothe R, Sherratt DJ, Leake MC. (2010)
Stoichiometry and architecture of active DNA replication machinery in Escherichia coli.
Science. 2010 Apr 23; 328(5977):498-501.
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Chivers CE, Crozat E, Chu C, Moy VT, Sherratt DJ, Howarth M. (2010)
A streptavidin variant with slower biotin dissociation and increased mechanostability.
Nat Methods. 2010 May;7(5):391-3.
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Crozat E, Meglio A, Allemand JF, Chivers CE, Howarth M, Vénien-Bryan C, Grainge I, Sherratt DJ. (2010)
Separating speed and ability to displace roadblocks during DNA translocation by FtsK.
EMBO J. 2010 Apr 21;29(8):1423-33.
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Sherratt DJ, Arciszewska LK, Crozat E, Graham JE, Grainge I. (2010)
The Escherichia coli DNA translocase FtsK.
Biochem Soc Trans. 2010 Apr;38(2):395-8. Review.
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Tran T, Sherratt DJ, Tolmasky ME. (2009)
fpr, a Deficient Xer Recombination Site from a Salmonella Plasmid Fails to Confer Stability by Dimer Resolution: Comparative Studies with the pJHCMW1 mwr site.
J Bact. Dec 4 [Epub ahead of print].
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Graham JE, Sivanathan V, Sherratt DJ, Arciszewska LK. (2009)
FtsK translocation on DNA stops at XerCD-dif.
Nucleic Acid Res. 2009 Oct 23 [Epub ahead of print].
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Trigueros S, Tran T, Sorto N, Newmark J, Colloms SD, Sherratt DJ, Tolmasky ME. (2009)
mwr Xer site-specific recombination is hypersensitive to DNA supercoiling.
Nucleic Acid Res. 37(11):3580-7.
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Liu X, Wang X, Reyes-Lamothe R, Sherratt DJ. (2009)
Replication-directed sister chromosome alignment in Escherichia coli.
Mol Microbiol. Aug 29 [Epub ahead of print].
→ For more listed on PubMed.
People
Research associate postdocs...
Technical staff...
Undergraduate students...
Recent former lab members...
Pictures
Contact
Enquiries with CV welcome. For postdoc or graduate student positions, please contact Prof. David Sherratt directly.
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Prof David Sherratt
Iveagh Professor of Microbiology
Tel: +44 (0)1865 613237
Fax: +44 (0)1865 613238
david.sherratt@bioch.ox.ac.uk -
Microbiology Unit
Department of Biochemistry
University of Oxford
South Parks Rd, Oxford
OX1 3QU, UK