title: A quantitative model of nucleosome dynamics.
abstract: The expression, replication and repair of eukaryotic genomes require the fundamental organizing unit of chromatin, the nucleosome, to be unwrapped and disassembled. We have developed a quantitative model of nucleosome dynamics which provides a fundamental understanding of these DNA processes. We calibrated this model using results from high precision single molecule nucleosome unzipping experiments, and then tested its predictions for experiments in which nucleosomes are disassembled by the DNA mismatch recognition complex hMSH2-hMSH6. We found that this calibrated model quantitatively describes hMSH2-hMSH6 induced disassembly rates of nucleosomes with two separate DNA sequences and four distinct histone modification states. In addition, this model provides mechanistic insight into nucleosome disassembly by hMSH2-hMSH6 and the influence of histone modifications on this disassembly reaction. This model's precise agreement with current experiments suggests that it can be applied more generally to provide important mechanistic understanding of the numerous nucleosome alterations that occur during DNA processing.
authors.affiliation: Department of Physics, The Ohio State University, 191 West Woodruff Avenue, Columbus, Ohio 43210-1117, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Forties
authors.forename: Justin A
authors.initials: JA
authors.lastname: North
authors.forename: Sarah
authors.initials: S
authors.lastname: Javaid
authors.forename: Omar P
authors.initials: OP
authors.lastname: Tabbaa
authors.forename: Richard
authors.initials: R
authors.lastname: Fishel
authors.forename: Michael G
authors.initials: MG
authors.lastname: Poirier
authors.forename: Ralf
authors.initials: R
authors.lastname: Bundschuh
mesh_terms: D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008957:Models, Genetic; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism; D011499:Protein Processing, Post-Translational
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D006657:Histones; D009707:Nucleosomes; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein