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.