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A multidisciplinary approach to the study of DNA enzymes down to the single molecule level

Objective

Many enzymes interacting with DNA locate their target sites by facilitated diffusion or DNA translocation driven by NTP hydrolysis. The focus of attention with such enzymes in the past has been on the processes of recognition and catalysis that occurs after the target has been located. What is presently lacking and urgently needed is a better understanding of the molecular mechanics of target location and how this is coupled to recognition and catalysis. It is proposed to investigate these questions for the important processes of DNA restriction and repair. Whereas simple restriction enzymes function as homodimers, more complex ones act in concert with other enzymes and depend on ATP hydrolysis. DNA mismatch repair is yet more complicated, and several protein s, some of them ATPases, need to be recruited in the early stages of the process. We need to understand what the molecular machinery of translocation looks like, and how the process is accomplished. Given the complexity of the systems and the mechanochemical processes under study, it will be necessary to deploy a variety of approaches and advanced techniques, not available in a single institution, to the problem.

The partners in the proposed network have been recruited from academia, research institutions and SMEs and selected on the strength of their expertise in the following areas: molecular biology, bioinformatics, enzymology, analytical chemistry, and biophysics. We are confident that with this array of interdisciplinary expertise we will be well placed to make substantial progress in understanding target site location, recognition and initiation of catalysis - issues of central importance for all enzymes acting on DNA. A thorough understanding of these systems will certainly enable better use to be made of them. We believe that young researchers trained in our network will greatly benefit from our integrated intersectorial approach and will be well placed for contemporary academic and industrial research.

Field of science

  • /natural sciences/chemical sciences/analytical chemistry
  • /natural sciences/biological sciences/genetics and heredity/dna
  • /natural sciences/biological sciences/molecular biology/structural biology
  • /natural sciences/biological sciences/biophysics
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes

Call for proposal

FP6-2004-MOBILITY-1
See other projects for this call

Funding Scheme

RTN - Marie Curie actions-Research Training Networks

Coordinator

JUSTUS-LIEBIG-UNIVERSITÄT
Address
Ludwigstrasse 23
Giessen
Germany

Participants (11)

UNIVERSITY OF BRISTOL
United Kingdom
Address
Senate House, Tyndall Avenue
Bristol
INSTITUTE OF ENZYMOLOGY - BIOLOGICAL RESEARCH CENTER - HUNGARIAN ACADEMY OF SCIENCES
Hungary
Address
Karolina Ut 29
Budapest
UNIVERSITY OF NEWCASTLE UPON TYNE
United Kingdom
Address
6 Kensington Terrace
Newcastle Upon Tyne
UNIVERSITY OF SOUTHERN DENMARK
Denmark
Address
Campusvej 55
Odense M
INSTITUTE OF BIOTECHNOLOGY
Lithuania
Address
V. Graiciuno 8
Vilnius
FERMENTAS UAB
Lithuania
Address
V. Graiciuno 8
Vilnius
INTERNATIONAL INSTITUTE OF MOLECULAR AND CELL BIOLOGY
Poland
Address
Ks. Trojdena 4
Warsaw
UNIVERSITY OF YORK
United Kingdom
Address
Heslington
York
REPLIZYME LIMITED
United Kingdom
Address
Genesis 2 Building, York Science Park
Heslington, York
CHARITE UNIVERSITÄTSMEDIZIN BERLIN
Germany
Address
Schumannstrasse 20-21
Berlin
HEINRICH-HEINE-UNIVERSITÄT DÜSSELDORF
Germany
Address
Universitätsstrasse 1
Düsseldorf