• norsk
    • English
  • English 
    • norsk
    • English
  • Login
View Item 
  •   Home
  • University of Bergen Library
  • Registrations from Cristin
  • View Item
  •   Home
  • University of Bergen Library
  • Registrations from Cristin
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Unrestrained ESCRT-III drives micronuclear catastrophe and chromosome fragmentation

Vietri, Marina; Schultz, Sebastian; Bellanger, Aurélie Nathalie Pascale; Jones, Carl; Petersen, Louise I; Raiborg, Camilla; Skarpen, Ellen; Pedurupillay Jesuthasan, Christeen Ramane; Kjos, Ingrid; Kip, Eline; Timmer, Ronny; Jain, Ashish; Collas, Philippe; Knorr, Roland; Grellscheid, Sushma; Kusumaatmaja, Halim; Brech, Andreas; Micci, Francesca; Stenmark, Harald Alfred; Campsteijn, Coen
Journal article, Peer reviewed
Accepted version
Thumbnail
View/Open
accepted version (61.44Mb)
URI
https://hdl.handle.net/11250/2771767
Date
2020
Metadata
Show full item record
Collections
  • Department of Biological Sciences [1843]
  • Registrations from Cristin [5665]
Original version
Nature Cell Biology. 2020, 22, 856-867.   10.1038/s41556-020-0537-5
Abstract
The ESCRT-III membrane fission machinery maintains the integrity of the nuclear envelope. Although primary nuclei resealing takes minutes, micronuclear envelope ruptures seem to be irreversible. Instead, micronuclear ruptures result in catastrophic membrane collapse and are associated with chromosome fragmentation and chromothripsis, complex chromosome rearrangements thought to be a major driving force in cancer development. Here we use a combination of live microscopy and electron tomography, as well as computer simulations, to uncover the mechanism underlying micronuclear collapse. We show that, due to their small size, micronuclei inherently lack the capacity of primary nuclei to restrict the accumulation of CHMP7–LEMD2, a compartmentalization sensor that detects loss of nuclear integrity. This causes unrestrained ESCRT-III accumulation, which drives extensive membrane deformation, DNA damage and chromosome fragmentation. Thus, the nuclear-integrity surveillance machinery is a double-edged sword, as its sensitivity ensures rapid repair at primary nuclei while causing unrestrained activity at ruptured micronuclei, with catastrophic consequences for genome stability.
Publisher
Nature Research
Journal
Nature Cell Biology
Copyright
Copyright 2021 Springer Nature Limited

Contact Us | Send Feedback

Privacy policy
DSpace software copyright © 2002-2019  DuraSpace

Service from  Unit
 

 

Browse

ArchiveCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDocument TypesJournalsThis CollectionBy Issue DateAuthorsTitlesSubjectsDocument TypesJournals

My Account

Login

Statistics

View Usage Statistics

Contact Us | Send Feedback

Privacy policy
DSpace software copyright © 2002-2019  DuraSpace

Service from  Unit