ESCRT-III-mediated membrane fusion drives chromosome fragments through nuclear envelope channels

J Cell Biol. 2020 Mar 2;219(3):e201905091. doi: 10.1083/jcb.201905091.

Abstract

Mitotic cells must form a single nucleus during telophase or exclude part of their genome as damage-prone micronuclei. While research has detailed how micronuclei arise from cells entering anaphase with lagging chromosomes, cellular mechanisms allowing late-segregating chromosomes to rejoin daughter nuclei remain underexplored. Here, we find that late-segregating acentric chromosome fragments that rejoin daughter nuclei are associated with nuclear membrane but devoid of lamin and nuclear pore complexes in Drosophila melanogaster. We show that acentrics pass through membrane-, lamin-, and nuclear pore-based channels in the nuclear envelope that extend and retract as acentrics enter nuclei. Membrane encompassing the acentrics fuses with the nuclear membrane, facilitating integration of the acentrics into newly formed nuclei. Fusion, mediated by the membrane fusion protein Comt/NSF and ESCRT-III components Shrub/CHMP4B and CHMP2B, facilitates reintegration of acentrics into nuclei. These results suggest a previously unsuspected role for membrane fusion, similar to nuclear repair, in the formation of a single nucleus during mitotic exit and the maintenance of genomic integrity.

Publication types

  • Research Support, N.I.H., Extramural
  • Video-Audio Media

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Chromosome Segregation*
  • Chromosomes, Insect*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Membrane Fusion*
  • Mitosis*
  • N-Ethylmaleimide-Sensitive Proteins / genetics
  • N-Ethylmaleimide-Sensitive Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / metabolism*
  • Nuclear Pore / genetics
  • Nuclear Pore / metabolism*
  • Signal Transduction
  • Time Factors
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism

Substances

  • CHMP2B protein, Drosophila
  • Drosophila Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Nerve Tissue Proteins
  • Shrb protein, Drosophila
  • Vesicular Transport Proteins
  • comt protein, Drosophila
  • N-Ethylmaleimide-Sensitive Proteins