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dc.contributor.author
Wienert, Beeke
dc.contributor.author
Nguyen, David N.
dc.contributor.author
Guenther, Alexis
dc.contributor.author
Feng, Sharon J.
dc.contributor.author
Locke, Melissa N.
dc.contributor.author
Wyman, Stacia K.
dc.contributor.author
Shin, Jiyung
dc.contributor.author
Kazane, Katelynn R.
dc.contributor.author
Gregory, Georgia L.
dc.contributor.author
Carter, Matthew A. M.
dc.contributor.author
Wright, Francis
dc.contributor.author
Conklin, Bruce R.
dc.contributor.author
Marson, Alex
dc.contributor.author
Richardson, Chris D.
dc.contributor.author
Corn, Jacob
dc.date.accessioned
2020-05-11T13:34:30Z
dc.date.available
2020-05-09T04:10:55Z
dc.date.available
2020-05-11T13:34:30Z
dc.date.issued
2020-12
dc.identifier.issn
2041-1723
dc.identifier.other
10.1038/s41467-020-15845-1
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/414004
dc.identifier.doi
10.3929/ethz-b-000414004
dc.description.abstract
Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2020-04-30
ethz.journal.title
Nature Communications
ethz.journal.volume
11
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
Nat Commun
ethz.pages.start
2109
en_US
ethz.size
15 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
::ETH Zürich::00002 - ETH Zürich
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::01559 - Lehre Biologie
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
2020-05-09T04:10:59Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2020-05-11T13:34:58Z
ethz.rosetta.lastUpdated
2021-02-15T10:57:40Z
ethz.rosetta.versionExported
true
ethz.COinS
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