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ESCRT-III–mediated membrane fusion drives chromosome fragments through nuclear envelope channels
Journal of Cell Biology ( IF 7.4 ) Pub Date : 2020-02-07 , DOI: 10.1083/jcb.201905091
Brandt Warecki 1 , Xi Ling 1 , Ian Bast 1 , William Sullivan 1
Affiliation  

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.

中文翻译:

ESCRT-III 介导的膜融合驱动染色体片段通过核膜通道

有丝分裂细胞必须在末期形成单个核,或者将其基因组的一部分排除为易于损伤的微核。虽然研究详细介绍了进入后期染色体滞后的细胞如何产生微核,但允许晚期分离染色体重新加入子核的细胞机制仍未得到充分探索。在这里,我们发现,在黑腹果蝇中,重新连接子核的晚期分离无着丝粒染色体片段与核膜相关,但缺乏核纤层蛋白和核孔复合体。我们发现,无着丝粒细胞穿过核膜中基于膜、核纤层蛋白和核孔的通道,当无着丝粒细胞进入细胞核时,这些通道会延伸和缩回。包围无着丝粒的膜与核膜融合,促进无着丝粒整合到新形成的细胞核中。由膜融合蛋白 Comt/NSF 和 ESCRT-III 成分 Shrub/CHMP4B 和 CHMP2B 介导的融合促进无着丝粒重新整合到细胞核中。这些结果表明,与核修复类似,膜融合在有丝分裂退出期间形成单核和维持基因组完整性方面具有先前未被怀疑的作用。
更新日期:2020-02-07
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