The Yeast INO80 Complex Operates as a Tunable DNA Length-Sensitive Switch to Regulate Nucleosome Sliding

Autor: Stephanie Johnson, Matthew J. Johnson, Sean L. Beckwith, Geeta J. Narlikar, Adam D. Longhurst, Ashby J. Morrison, Laura J. Lee, Coral Y. Zhou
Rok vydání: 2018
Předmět:
DNA Replication
0301 basic medicine
Saccharomyces cerevisiae Proteins
DNA Repair
enzymology
1.1 Normal biological development and functioning
Saccharomyces cerevisiae
Biology
single-molecule FRET
Medical and Health Sciences
INO80
Article
Histones
DNA length sensing
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Underpinning research
Genetics
Nucleosome
Ino80 complex
DNA
Fungal

Molecular Biology
INO80 chromatin remodeling complex
Nucleosome sliding
High Mobility Group Proteins
DNA
ATP-dependent chromatin-remodeling enzyme
Cell Biology
Single-molecule FRET
Biological Sciences
Chromatin Assembly and Disassembly
DNA Damage Repair
Yeast
Nucleosomes
Cell biology
Fungal
030104 developmental biology
chemistry
Generic health relevance
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Molecular cell, vol 69, iss 4
ISSN: 1097-2765
Popis: The yeast INO80 chromatin remodeling complex plays essential roles in regulating DNA damage repair, replication, and promoter architecture. INO80's role in these processes is likely related to its ability to slide nucleosomes, but the underlying mechanism is poorly understood. Here we use ensemble and single-molecule enzymology to study INO80-catalyzed nucleosome sliding. We find that the rate of nucleosome sliding by INO80 increases ∼100-fold when the flanking DNA length is increased from 40 to 60bp. Furthermore, once sliding is initiated, INO80 moves the nucleosome rapidly at least 20bp without pausing to re-assess flanking DNA length, and it can change the direction of nucleosome sliding without dissociation. Finally, we show that the Nhp10 module of INO80 plays an auto-inhibitory role, tuning INO80's switch-like response to flanking DNA. Our results indicate that INO80 is a highly processive remodeling motor that is tightly regulated by both substrate cues and non-catalytic subunits.
Databáze: OpenAIRE