CPM Seminar

Protein-DNA search and recognition: p53 as a case study

Jason Leith

Program in Biophysics
Harvard University

Transcription factors (TFs) must locate and bind to their recognition sequences both speedily and stably. Alternating rounds of 3D diffusion in solution and 1D diffusion along DNA has been proposed as a means by which their search process may be facilitated. For this facilitation to be effective, TFs must be able while undergoing 1D diffusion on DNA both to slide quickly and to read its sequence. We offer a model in which TFs bind to DNA in multiple modes that explains how they can achieve this. We further present evidence that the human tumor suppressor p53's diffusional kinetics are sequence-dependent in a way accounted for by the model, and thus that it indeed can read the DNA sequence it is rapidly translocating along.