CDK1 controls CHMP7-dependent nuclear envelope reformation

Through the process of annular fusion and disassembly of spindle microtubules, the Endosomal Sorting Complex Required for Transport-III (ESCRT-III) machinery has emerged as a key player in the regeneration of a sealed nuclear envelope during mitotic exit, and in the repair of this organelle during interphase rupture. ESCRT-III polymerisation at the nuclear envelope occurs transiently during mitotic exit and CHMP7, an ER-localised ESCRT-II/ESCRT-III hybrid protein, initiates assembly in a manner dependent upon the INM protein LEM2. Whilst classical nucleocytoplasmic transport mechanisms have been proposed to separate LEM2 and CHMP7 during interphase, it is unclear how CHMP7 assembly is suppressed in mitosis when NE and ER identities are mixed. Here, we use live cell imaging and protein biochemistry to examine the biology of these proteins during mitotic exit. We show that CHMP7 plays an important role in disaggregating LEM2 clusters at the reforming nuclear envelope during mitotic exit to allow proper nuclear regeneration. Further, we show that CDK1 phosphorylates CHMP7 upon mitotic entry and suppresses its polymerisation, preventing its inappropriate capture of LEM2 in the peripheral ER during mitotic exit. Lastly, we establish that a microtubule network is dispensable for ESCRT-III assembly at the reforming nuclear envelope. These data identify a key cell-cycle control programme allowing ESCRT-III-dependent nuclear regeneration.