DNA is damaged continuously by agents that occur naturally within our cells as well as by exogenous factors such as high-energy radiation. In addition to the diverse damage introduced into previously ”healthy” DNA, the replication process itself causes errors in the genetic code (for instance base-base mis-pairs). If unrepaired, such damage and errors in the DNA can lead to cell death or diseases such as cancers. To maintain genomic stability, a number of DNA repair mechanisms have evolved, such as base-excision repair (BER), nucleotide-excision repair (NER), recombinational repair, mismatch repair (MMR), and direct damage reversal. These DNA repair systems each target different types of DNA damage and many of them are evolutionary conserved.

Single molecule studies of DNA repair

We use atomic force microscopy (AFM) in combination with other biophysical and biochemical techniques to study protein-DNA complexes involved in DNA repair. AFM enables us to directly visualize molecular assemblies at the level of the individual molecules. We are particularly interested in understanding the different DNA damage recognition strategies developed by the various DNA repair mechanisms. A second focus in our laboratory is the advancement of AFM to allow access to increased information on the sample. In this context, we are developing a combined fluorescence-AFM system for high resolution imaging of multi-protein complexes. 

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