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dc.contributor.author
Ferretti, Lorenza P.
dc.contributor.author
Himmels, Sarah-Felicitas
dc.contributor.author
Trenner, Anika
dc.contributor.author
Walker, Christina
dc.contributor.author
Von Aesch, Christine
dc.contributor.author
Eggenschwiler, Aline
dc.contributor.author
Murina, Olga
dc.contributor.author
Enchev, Radoslav I.
dc.contributor.author
Peter, Matthias
dc.contributor.author
Freire, Raimundo
dc.contributor.author
Porro, Antonio
dc.contributor.author
Sartori, Alessandro A.
dc.date.accessioned
2018-09-07T12:05:24Z
dc.date.available
2017-06-12T13:38:48Z
dc.date.available
2018-09-07T12:05:24Z
dc.date.issued
2016-08
dc.identifier.issn
2041-1723
dc.identifier.other
10.1038/ncomms12628
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/121195
dc.identifier.doi
10.3929/ethz-b-000121195
dc.description.abstract
Human CtIP is a decisive factor in DNA double-strand break repair pathway choice by enabling DNA-end resection, the first step that differentiates homologous recombination (HR) from non-homologous end-joining (NHEJ). To coordinate appropriate and timely execution of DNA-end resection, CtIP function is tightly controlled by multiple protein–protein interactions and post-translational modifications. Here, we identify the Cullin3 E3 ligase substrate adaptor Kelch-like protein 15 (KLHL15) as a new interaction partner of CtIP and show that KLHL15 promotes CtIP protein turnover via the ubiquitin-proteasome pathway. A tripeptide motif (FRY) conserved across vertebrate CtIP proteins is essential for KLHL15-binding; its mutation blocks KLHL15-dependent CtIP ubiquitination and degradation. Consequently, DNA-end resection is strongly attenuated in cells overexpressing KLHL15 but amplified in cells either expressing a CtIP-FRY mutant or lacking KLHL15, thus impacting the balance between HR and NHEJ. Collectively, our findings underline the key importance and high complexity of CtIP modulation for genome integrity.
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
Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnover to fine-tune DNA-end resection
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2016-08-26
ethz.journal.title
Nature Communications
ethz.journal.volume
7
en_US
ethz.journal.abbreviated
Nat Commun
ethz.pages.start
12628
en_US
ethz.size
16 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
007044158
ethz.publication.place
London
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::02517 - Institut für Biochemie / Institute of Biochemistry (IBC)::03595 - Peter, Matthias / Peter, Matthias
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02517 - Institut für Biochemie / Institute of Biochemistry (IBC)::03595 - Peter, Matthias / Peter, Matthias
ethz.date.deposited
2017-06-12T13:45:00Z
ethz.source
ECIT
ethz.identifier.importid
imp593654c2063c123482
ethz.ecitpid
pub:183286
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-15T03:36:35Z
ethz.rosetta.lastUpdated
2019-02-03T07:47:12Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=Cullin3-KLHL15%20ubiquitin%20ligase%20mediates%20CtIP%20protein%20turnover%20to%20fine-tune%20DNA-end%20resection&rft.jtitle=Nature%20Communications&rft.date=2016-08&rft.volume=7&rft.spage=12628&rft.issn=2041-1723&rft.au=Ferretti,%20Lorenza%20P.&Himmels,%20Sarah-Felicitas&Trenner,%20Anika&Walker,%20Christina&Von%20Aesch,%20Christine&rft.genre=article&
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