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Unrestrained ESCRT-III drives micronuclear catastrophe and chromosome fragmentation

Vietri, Marina; Schultz, Sebastian W.; Bellanger, Aurélie; Jones, Carl M.; Petersen, Louise I.; Raiborg, Camilla; Skarpen, Ellen; Pedurupillay, Christeen Ramane J.; Kjos, Ingrid; Kip, Eline; Timmer, Romy; Jain, Ashish; Collas, Philippe; Knorr, Roland L.; Grellscheid, Sushma N.; Kusumaatmaja, Halim; Brech, Andreas; Micci, Francesca; Stenmark, Harald; Campsteijn, Coen

Unrestrained ESCRT-III drives micronuclear catastrophe and chromosome fragmentation Thumbnail


Marina Vietri

Sebastian W. Schultz

Aurélie Bellanger

Carl M. Jones

Louise I. Petersen

Camilla Raiborg

Ellen Skarpen

Christeen Ramane J. Pedurupillay

Ingrid Kjos

Eline Kip

Romy Timmer

Ashish Jain

Philippe Collas

Roland L. Knorr

Andreas Brech

Francesca Micci

Harald Stenmark

Coen Campsteijn


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.


Vietri, M., Schultz, S. W., Bellanger, A., Jones, C. M., Petersen, L. I., Raiborg, C., …Campsteijn, C. (2020). Unrestrained ESCRT-III drives micronuclear catastrophe and chromosome fragmentation. Nature Cell Biology, 22(7), 856-867.

Journal Article Type Article
Acceptance Date May 24, 2020
Online Publication Date Jun 29, 2020
Publication Date 2020
Deposit Date Jul 9, 2020
Publicly Available Date Dec 29, 2020
Journal Nature Cell Biology
Print ISSN 1465-7392
Electronic ISSN 1476-4679
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 22
Issue 7
Pages 856-867


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