Spastin and ESCRT-III

During cell division, the nuclear envelope breaks down so that duplicated chromosomes can be separated by the microtubule-containing spindle apparatus. Upon completion of this process, in anaphase, new nuclear envelopes are formed around the two daughter nuclei, and the mitotic spindle is disassembled by a mechanism that has not been known.

We uncovered a mechanism whereby ESCRT proteins coordinate nuclear envelope sealing and mitotic spindle disassembly. The ESCRT machinery assembles into filaments at holes of the reforming nuclear envelope that are intersected by microtubule cables of the mitotic spindle. Here ESCRT coordinates the removal of the microtubule cables, by recruiting the enzyme Spastin, and the closure of the remaining holes.

By interfering with normal ESCRT function during anaphase, we observe that DNA becomes damaged, indicating that the novel mechanism of spindle disassembly and nuclear envelope sealing is important for keeping our genome safe.

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