Protein-DNA interaction, random walks and polymer statistics

In Part I of the thesis, a general physical framework describing the kinetics of protein- DNA interaction is developed. Recognition and binding of specific sites on DNA by proteins is central for many cellular functions such as transcription, replication, and recombination. In the process of recognition, a protein rapidly searches for its specific site on a long DNA molecule and then strongly binds this site. Earlier studies have suggested that rapid search involves sliding of the protein along the DNA. I treat sliding as a one-dimensional diffusion in a sequence-dependent rough energy landscape. I demonstrate that, despite the landscape's roughness, rapid search can. be achieved if one-dimensional sliding is accompanied by three-dimensional diffusion. I estimate the range of the specific and nonspecific DNA-binding energy required for rapid search and suggest experiments that can test the proposed mechanism. It appears that realistic energy functions cannot provide both rapid search and strong binding of a rigid protein. To reconcile these two fundamental requirements, a search-and-fold mechanism is proposed that involves the coupling of protein binding and partial protein folding. In this regard, I propose an effective energy landscape that incorporates longitudinal (sliding) and transversal (folding) dynamics. I also study the influence of finite correlation length in the binding potential profile on the one-dimensional diffusion. The proposed mechanism has several important biological implications for search in the presence of other proteins and nucleosomes, simultaneous search by several proteins, etc.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Physics.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Slutsky, Michael

Advisor dc:contributor.advisor

• Leonid A. Mirny.

• Physics.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/32295

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/32295