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 |
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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 |
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