Nucleosome stability and accessibility of its DNA to proteins.
In this paper we present a theoretical description of the accessibility of nucleosomal DNA to proteins. We reassess the classical analysis of Polach and Widom (1995) who demonstrated that proteins (in their case restriction enzymes) gain access to buried binding sites inside a nucleosome through spontaneous unwrapping of DNA from the protein spool. We introduce a straightforward nucleosome model the predictions of which show good agreement with experimental data. By fitting the model to the data we obtain the values of two quantities: the adsorption energy to the histone octamer per length of DNA and the extra length that the DNA needs to unwrap beyond the binding site of an enzyme before the enzyme can act as effectively as on bare DNA. Our results indicate that the effective binding energy is surprisingly low which suggests that the nucleosomal parameters are tuned such that two large energies, the DNA bending energy and the pure adsorption energy, nearly cancel. This paper is based on a lecture presented at the summer school "DNA and Chromosomes 2009: Physical and Biological Applications". We follow the lecture as closely as possible which is why we spend more time than usual on issues that are already well-known in the field, and why we discuss some well-known results from a different perspective.
Prinsen
Peter
P
Instituut Lorentz, Universiteit Leiden, P.O. Box 9506, 2300 RA Leiden, The Netherlands.
Schiessel
Helmut
H
D000465:Algorithms; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004262:DNA Restriction Enzymes / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
D006657:Histones; D009707:Nucleosomes; D011506:Proteins; D004247:DNA; D004262:DNA Restriction Enzymes