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
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