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Structure and regulation of the human INO80–nucleosome complex

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Title: Structure and regulation of the human INO80–nucleosome complex
Authors: Ayala, R
Willhoft, O
Aramayo, R
Wilkinson, M
McCormack, E
Ocloo, L
Wigley, D
Zhang, X
Item Type: Journal Article
Abstract: Access to DNA within nucleosomes is required for a variety of processes in cells including transcription, replication and repair. Consequently, cells encode multiple systems that remodel nucleosomes. These complexes can be simple, involving one or a few protein subunits, or more complicated multi-subunit machines1. Biochemical studies2-4 have placed the motor domains of several remodellers on the superhelical location (SHL) 2 region of the nucleosome. Structural studies on Chd1 and Snf2 (RSC) in complex with nucleosomes5-7 have provided insights into the basic mechanism of nucleosome sliding by these complexes. However, how larger, multi-subunit remodelling complexes, such as INO80, interact with nucleosomes or how remodellers carry out functions such as nucleosome sliding8, histone exchange9, and nucleosome spacing10-12 remains poorly understood. Although some remodellers work as monomers13, others work as highly cooperative dimers11,14,15. Here we present the structure of the INO80 chromatin remodeller with a bound nucleosome revealing that INO80 interacts with nucleosomes in a unique manner with the motor domains located at the entry point to the wrap around the histone core rather than at SHL2. The Arp5-Ies6 module of INO80 makes additional contacts on the opposite side of the nucleosome. This unique arrangement allows the H3 tails of the nucleosome to play a role in regulation, differing from other characterised remodellers.
Issue Date: 11-Apr-2018
Date of Acceptance: 16-Feb-2018
URI: http://hdl.handle.net/10044/1/58477
DOI: https://dx.doi.org/10.1038/s41586-018-0021-6
ISSN: 0028-0836
Publisher: Nature Publishing Group
Start Page: 391
End Page: 395
Journal / Book Title: Nature
Volume: 556
Copyright Statement: © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Sponsor/Funder: Wellcome Trust
Wellcome Trust
Wellcome Trust
Wellcome Trust
Cancer Research UK
Cancer Research UK
Wellcome Trust
Funder's Grant Number: 091093/B/09/Z
098412/Z/12/Z
WT/099128/Z/12/Z
095519/B/11/Z
12799
C6913/A21608
209327/Z/17/Z
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CHROMATIN-REMODELING COMPLEX
EM STRUCTURE DETERMINATION
CRYO-EM
NUCLEOSOME COMPLEX
DNA
ISWI
MECHANISM
PARTICLE
TRANSLOCATION
RESOLUTION
Actins
DNA Helicases
DNA-Binding Proteins
Histones
Humans
Microfilament Proteins
Models, Molecular
Multiprotein Complexes
Nucleosomes
Protein Domains
Ubiquitin-Protein Ligases
MD Multidisciplinary
General Science & Technology
Publication Status: Published
Online Publication Date: 2018-04-11
Appears in Collections:Department of Medicine
Faculty of Medicine



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