Stephen C. Kowalczykowski

I am interested in the chemistry and physics of life processes. I have focused on the biochemical mechanisms by which DNA is copied and maintained. DNA is broken almost every time a cell divides. Preservation of genetic information requires the repair of such DNA breaks, a chromosomal "restoration" that occurs by genetic recombination. My laboratory studies the biochemistry of recombinational DNA repair in prokaryotes, eukaryotes, and archaea. DNA recombination requires many protein machines acting in concert. We study proteins responsible for recognition of DNA sequence homology and exchange of DNA strands (RecA, Rad51, RadA); for annealing complementary strands of DNA (Rec0, Rad52, Rad59); for processing DNA breaks (RecBCD, RecQ?helicases); and for accelerating assembly and disassembly of the recombination machinery (RecFOR, Rad52, Rad54, RecQ?helicases, Srs2). Recently, we developed biophysical methods to visualize single molecules of these proteins in action - "visual biochemistry". This is achieved using a laser to trap an individual DNA molecule. Then, using fluorescence and microscopic imaging, we can visualize DNA motor proteins translocating along DNA strands - their "tracks". We also can build assemblies of individual proteins, one molecule at a time, on single DNA molecules to see their unique, rather than collective, dynamic behavior in real-time.