Research Friedhoff
Friedhoff
Molecular enzymology of the DNA mismatch repair (MMR) pathway
The repair of DNA damage is a critical step in maintenance of genome integrity. Errors in DNA repair pathways lead to build up of mutations, genome instability and ultimately result in cancer in humans. The processes involved are executed by complicated molecular machines that execute a carefully choreographed set of activation steps.
We study molecular enzymology of the evolutionary conserved DNA mismatch repair (MMR) pathway from Escherichia coli. To study this dynamic multistep repair pathway we use complementary approaches employing enzymatic, biochemical and biophysical methods to study the protein-nucleic acid and protein-protein interactions (endonuclease, ATPase, helicase). Typical biophysical methods comprise fluorescence spectroscopy (e.g. FRET - steady-state and time-resolved (stopped-flow)), chemical cross-linking (combined with mass spectrometry), interaction analysis (ITC), dynamic light scattering, circular dichroism. In national and international collaborations we combine single molecule analysis, high resolution structural biology and highly time-resolved biochemical and biophysical assays that will allow an integrated vision of the steps in DNA mismatch repair (MMR).
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