Show simple item record

dc.contributor.author
Kilic, Sinan
dc.contributor.author
Lezaja, Aleksandra
dc.contributor.author
Gatti, Marco
dc.contributor.author
Bianco, Eliana
dc.contributor.author
Michelena, Jone
dc.contributor.author
Imhof, Ralph
dc.contributor.author
Altmeyer, Matthias
dc.date.accessioned
2019-09-02T08:45:38Z
dc.date.available
2019-09-01T02:10:23Z
dc.date.available
2019-09-02T08:34:58Z
dc.date.available
2019-09-02T08:45:38Z
dc.date.issued
2019-08-15
dc.identifier.other
10.15252/embj.2018101379
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/361684
dc.identifier.doi
10.3929/ethz-b-000361684
dc.description.abstract
The DNA damage response (DDR) generates transient repair compartments to concentrate repair proteins and activate signaling factors. The physicochemical properties of these spatially confined compartments and their function remain poorly understood. Here, we establish, based on live cell microscopy and CRISPR/Cas9‐mediated endogenous protein tagging, that 53BP1‐marked repair compartments are dynamic, show droplet‐like behavior, and undergo frequent fusion and fission events. 53BP1 assembly, but not the upstream accumulation of γH2AX and MDC1, is highly sensitive to changes in osmotic pressure, temperature, salt concentration and to disruption of hydrophobic interactions. Phase separation of 53BP1 is substantiated by optoDroplet experiments, which further allowed dissection of the 53BP1 sequence elements that cooperate for light‐induced clustering. Moreover, we found the tumor suppressor protein p53 to be enriched within 53BP1 optoDroplets, and conditions that disrupt 53BP1 phase separation impair 53BP1‐dependent induction of p53 and diminish p53 target gene expression. We thus suggest that 53BP1 phase separation integrates localized DNA damage recognition and repair factor assembly with global p53‐dependent gene activation and cell fate decisions.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Wiley
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
53BP1
en_US
dc.subject
DNA damage response
en_US
dc.subject
genome stability
en_US
dc.subject
liquid–liquid phase separation
en_US
dc.subject
p53
en_US
dc.title
Phase separation of 53BP1 determines liquid-like behavior of DNA repair compartments
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2019-07-01
ethz.journal.title
The EMBO Journal
ethz.journal.volume
38
en_US
ethz.journal.issue
16
en_US
ethz.pages.start
e101379
en_US
ethz.size
17 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.publication.place
Weinheim
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2019-09-01T02:10:26Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-09-02T08:35:10Z
ethz.rosetta.lastUpdated
2019-09-02T08:45:50Z
ethz.rosetta.versionExported
true
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=Phase%20separation%20of%2053BP1%20determines%20liquid-like%20behavior%20of%20DNA%20repair%20compartments&rft.jtitle=The%20EMBO%20Journal&rft.date=2019-08-15&rft.volume=38&rft.issue=16&rft.spage=e101379&rft.au=Kilic,%20Sinan&Lezaja,%20Aleksandra&Gatti,%20Marco&Bianco,%20Eliana&Michelena,%20Jone&rft.genre=article&
 Search via SFX

Files in this item

Thumbnail

Publication type

Show simple item record