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Components of an ESCRT-independent nuclear envelope assembly pathway

Sydir, E. M.; Farra, M. H.; Whitford, A. L.; Hinojosa, S.; Kao, P.-Y.; Paulo, J. A.; Swarup, S.; Lusk, C. P.; Harper, J. W.; Lee, I.-J.; Pellman, D.

2026-02-03 cell biology
10.64898/2026.02.01.703137 bioRxiv
Show abstract

Following chromosome segregation, the nuclear envelope (NE) must be reassembled and holes in the nuclear membrane must be "sealed." During NE assembly, the NE-specific adaptor, Cmp7, recruits/activates ESCRT-III proteins to mediate NE sealing. However, recent evidence suggests the presence of alternative mechanisms. In a screen using the fission yeast, S. japonicus, we recently implicated the ESCRT adaptor, Alx1, and a conserved, but little studied protein, Vid27, in Cmp7-independent NE assembly. Here, we provide direct evidence that Alx1 functions in a Cmp7- and ESCRT-independent NE assembly pathway via positive regulation of Vid27. Consistent with a role in membrane remodeling, Vid27 localizes to sites of postmitotic NE sealing and is essential in S. japonicus. Alx1 and Vid27 form a complex and mutations disrupting their interaction abolish Alx1s enhancement of Vid27 function at the NE. These findings define components of a new Cmp7- and ESCRT-independent NE assembly pathway, advancing our understanding of the mechanisms crucial for maintaining the integrity of the nucleus.

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