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dc.contributor.author
Wang, Alan S.
dc.contributor.author
Chen, Leo C.
dc.contributor.author
Wu, R. Alex
dc.contributor.author
Hao, Yvonne
dc.contributor.author
McSwiggen, David T.
dc.contributor.author
Heckert, Alec B.
dc.contributor.author
Richardson, Christopher D.
dc.contributor.author
Gowen, Benjamin G.
dc.contributor.author
Kazane, Katelynn R.
dc.contributor.author
Vu, Jonathan T.
dc.contributor.author
Wyman, Stacia K.
dc.contributor.author
Shin, Jiyung J.
dc.contributor.author
Darzacq, Xavier
dc.contributor.author
Walter, Johannes C.
dc.contributor.author
Corn, Jacob E.
dc.date.accessioned
2020-07-30T17:41:11Z
dc.date.available
2020-07-19T02:52:18Z
dc.date.available
2020-07-30T17:41:11Z
dc.date.issued
2020-07-16
dc.identifier.issn
1097-2765
dc.identifier.issn
1097-4164
dc.identifier.other
10.1016/j.molcel.2020.06.014
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/426931
dc.description.abstract
Cas9 is a prokaryotic RNA-guided DNA endonuclease that binds substrates tightly in vitro but turns over rapidly when used to manipulate genomes in eukaryotic cells. Little is known about the factors responsible for dislodging Cas9 or how they influence genome engineering. Unbiased detection through proximity labeling of transient protein interactions in cell-free Xenopus laevis egg extract identified the dimeric histone chaperone facilitates chromatin transcription (FACT) as an interactor of substrate-bound Cas9. FACT is both necessary and sufficient to displace dCas9, and FACT immunodepletion converts Cas9’s activity from multi-turnover to single turnover. In human cells, FACT depletion extends dCas9 residence times, delays genome editing, and alters the balance between indel formation and homology-directed repair. FACT knockdown also increases epigenetic marking by dCas9-based transcriptional effectors with a concomitant enhancement of transcriptional modulation. FACT thus shapes the intrinsic cellular response to Cas9-based genome manipulation most likely by determining Cas9 residence times.
en_US
dc.language.iso
en
en_US
dc.publisher
Cell Press
en_US
dc.title
The Histone Chaperone FACT Induces Cas9 Multi-turnover Behavior and Modifies Genome Manipulation in Human Cells
en_US
dc.type
Journal Article
dc.date.published
2020-06-29
ethz.journal.title
Molecular Cell
ethz.journal.volume
79
en_US
ethz.journal.issue
2
en_US
ethz.journal.abbreviated
Mol Cell
ethz.pages.start
221
en_US
ethz.pages.end
233.e5
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Cambridge, MA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::09635 - Corn, Jacob / Corn, Jacob
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::09635 - Corn, Jacob / Corn, Jacob
ethz.date.deposited
2020-07-19T02:52:22Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Metadata only
en_US
ethz.rosetta.installDate
2020-07-30T17:41:28Z
ethz.rosetta.lastUpdated
2021-02-15T15:45:52Z
ethz.rosetta.versionExported
true
ethz.COinS
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