A method of observing individual DNA molecules in live cells is described. The technique is based on the binding of a fluorescently tagged lac repressor protein to binding sites engineered into the DNA of interest. This method can be adapted to follow many recombinant DNAs in live cells over time.
Norby, K., Chiu, Y., Sugden, B. Monitoring Plasmid Replication in Live Mammalian Cells over Multiple Generations by Fluorescence Microscopy. J. Vis. Exp. (70), e4305, doi:10.3791/4305 (2012).