Dynamic interactions of p53 with DNA in solution by time-lapse atomic force microscopy

Dynamic interactions of the tumor suppressor protein p53 with a DNA fragmen t containing a p53-specific recognition sequence were directly observed by time-lapse tapping mode atomic force microscopy (AFM) in liquid. The divale nt cation Mg2+ was used to loosely attach both DNA and p53 to a mica surfac e so they could be imaged by the AFM while interacting with each other. Var ious interactions of p53 with DNA were observed, including dissociation/re- association, sliding and possibly direct binding to the specific sequence. Two modes of target recognition of p53 were detected: (a) direct binding, a nd (b) initial non-specific binding with subsequent translocation by one-di mensional diffusion of the protein along the DNA to the specific site. (C) 2001 Academic Press.