Key achievements

The group studies cell cycle control in simple model organisms and has made significant contributions toward understanding the molecular mechanisms involved in regulation of DNA replication in Escherichia coli.

Major research achievements include the following:

  • The first demonstration that flow cytometry could be used to analyze the bacterial cell cycle (J. Bacteriol.154:656-662: 1983).
  • Complete theoretical framework for the analysis of DNA distributions of bacterial cells with overlapping replication cycles, and a method for determination of cell cycle periods by computer simulation (J. Bacteriol.163: 661-668: 1985).
  • The first direct demonstration that initiation of chromosome replication in E. coli occurs simultanously at all orgins, and a method for determining the number of origins per cell and the degree of initiation synchrony (EMBO J.5: 1711-1717: 1986).
  • Identification of DnaA as a regulator of initiation frequency (Cell 57: 881-889: 1989). Structural requirements for strand opening at the origin (EMBO J. 9:2341-2348: 1990).
  • Discovery of the origin binding protein, Rob (J. Biol. Chem.268:5365-5370: 1993).
  • Demonstration of opposing roles for DnaA and SeqA in regulation of the cell cycle (PNAS 93: 12206-12211: 1996).
  • Demonstration of inhibition of  chromosome replication by SeqA in an in vitro replication system(EMBO J.17: 4158-4165: 1998).
  • Demonstration of effects of SeqA on strand opening (EMBO J. 18: 4882-4888: 1999) and chromosome segregation (EMBO J. 22: 315-323: 2003).
  • Characterization of SeqA mutants and the connection between sequestration and sister chromosome organization (Mol. Microbiol.47:619-32: 2003).
  • Lack of DnaA protein affects replication fork stability and cell division (Mol. Microbiol.50:349-362: 2004).
  • The requirement for acidic phospholipids to initiate replication could be bypassed by mutations in the C-terminus of DnaA(EMBO J. 20: 1164-1172: 2001).
  • Determination of the basis for origin compatibility in E. coli. (EMBO J. 22: 140-150: 2003). Construction of a non-sequesterable origin and finding that re-replication from such origins generates three-nucleoid cells which divide asymmetrically (Mol. Microbiol. 51: 1589-600:2004).
  • Model for the multimerization of SeqA dimers into a left handed helical fiber (Mol. Microbiol. 54:123-31: 2004 and Genes to Cells10:1039-1049: 2005).
  • Model for the higher-order organization of replisomes into hyperstructures (Mol Microbiol52:1597-612: 2004).
  • Definition of the requirements for the sequestration mechanism (Mol. Microbiol. 51:1589-600: 2004, J. Mol Biol. 350: 7-11: 2005 and J Mol Biol 384:1076-1085: 2008).
  • Discovery of a novel regulatory mechanism that couples deoxyribonucleotide synthesis and DNA replication (EMBO J25: 1137-47: 2006).
  • Demonstration of origin colocalization during growth with overlapping replication cycles (EMBO J26:4514-4522: 2007).
  • Demonstration that the DnaA protein interacts with RNA polymerase (Mol Microbiol. 71:1018-1030: 2009).
  • Determination of the behaviour of replication forks during depletion of nucleotides (PLoS ONE 4(10):e7617: 2009).
  • Model for the organization of new DNA in rapidly growing cells (Genes to Cells14: 643-657: 2009; Nucleic Acids Res 40:5465-76, 2012, PLoS One. 9(10):e110575, 2014).  
  • Discovery of a new role for the processivity factor (sliding clamp) of the replicative polymerase (Mol Microbiol 79: 433-46: 2011).
  • Discovery of a new role for the transcription factor Fis (PLoS One, 8 (12), e83562, 2013).
  • Characterization of DNA compaction during the SOS response and demonstration of its dependence on the RecN and RecA proteins Microbiology 160(Pt 5):872-82, 2014).
  • Discovery of the stabilized stretch of DNA between the replisome and the SeqA structure (Nucleic Acids Res 43(5):2730-43, 2015).
  • Definition of the prokaryotic cell cycle “machine” as being driven by the production and cycling of ATP-DnaA to ADP-DnaA and disproof of DnaA as the limiting factor (PLoS Genetics 11 (6),e1005276, 2015).
  • Characterization of DNA organization by the H-NS protein during replication, and its importance for cell physiology during rapid growth conditions (J Bacteriol 198(8): 1305-1316, 2016)
 
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