Catalytic Mechanism of the INO80 Chromatin Remodeler Acting on the Nucleosome

Abstract

Elucidation of the mechanisms that control chromatin dynamics and changes in chromatin structure is crucial to understand how DNA accessibility is governed in eukaryotes. ATP-dependent chromatin remodelers balance DNA accessibility and densely packed nucleosomes. In this regard, the multi-subunit INO80 remodeler complex (INO80 complex) plays an important but yet largely elusive role in all DNA metabolic processes such as transcription, DNA replication and DNA damage repair in vivo. This study dissects how the INO80 complex remodels nucleosomes on the molecular level. Nucleosome remodeling assays that combine bulk biochemistry with single-molecule Fluorescence Resonance Energy Transfer (FRET) methods allow the decomposition and modulation of the remodeling catalytic cycle of the INO80 complex. These mechanistic insights on the INO80 complex contribute to understand the fundamentals of chromatin remodeling catalysis. In the light of emerging data on other remodeling systems the catalytic activity of the INO80 complex plays an important role in transcription regulation and genome maintenance.