title: Reaction cycle of the yeast Isw2 chromatin remodeling complex.
abstract: Members of the ISWI family of chromatin remodeling factors hydrolyze ATP to reposition nucleosomes along DNA. Here we show that the yeast Isw2 complex interacts with DNA in a nucleotide-dependent manner at physiological ionic strength. Isw2 efficiently binds DNA in the absence of nucleotides and in the presence of a nonhydrolyzable ATP analog. Conversely, ADP promotes the dissociation of Isw2 from DNA. In contrast, Isw2 remains bound to mononucleosomes through multiple cycles of ATP hydrolysis. Solution studies show that Isw2 undergoes nucleotide-dependent alterations in conformation not requiring ATP hydrolysis. Our results indicate that during an Isw2 remodeling reaction, hydrolysis of successive ATP molecules coincides with cycles of DNA binding, release, and rebinding involving elements of Isw2 distinct from those interacting with nucleosomes. We propose that progression of the DNA-binding site occurs while nucleosome core contacts are maintained and generates a force dissipated by disruption of histone-DNA interactions.
authors.affiliation: ETH Zürich, Institut für Molekularbiologie und Biophysik, ETH-Hönggerberg HPK, Zürich, Switzerland.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Fitzgerald
authors.forename: Carl
authors.initials: C
authors.lastname: DeLuca
authors.forename: Imre
authors.initials: I
authors.lastname: Berger
authors.forename: Hélène
authors.initials: H
authors.lastname: Gaillard
authors.forename: Raphael
authors.initials: R
authors.lastname: Sigrist
authors.forename: Kyoko
authors.initials: K
authors.lastname: Schimmele
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Richmond
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000502:physiology; D009707:Nucleosomes / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D004271:DNA, Fungal; D006657:Histones; C086468:ISWI protein; D009707:Nucleosomes; D014157:Transcription Factors; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases