In most animal cell types, the interphase nucleus is largely disassembled during mitotic entry. The nuclear envelope breaks down and chromosomes are compacted into separated masses. Chromatin organization is also mostly lost and kinetochores assemble on centromeres. Mitotic protein kinases play several roles in inducing these transformations by phosphorylating multiple effector proteins. In many of these events, the mechanistic consequences of phosphorylation have been characterized. In comparison, how the nucleus reassembles at the end of mitosis is less well understood in mechanistic terms. In recent years, much progress has been made in deciphering how dephosphorylation of several effector proteins promotes nuclear envelope reassembly, chromosome decondensation, kinetochore disassembly and interphase chromatin organization. The precise roles of protein phosphatases in this process, in particular of the PP1 and PP2A groups, are emerging. Moreover, how these enzymes are temporally and spatially regulated to ensure that nuclear reassembly progresses in a coordinated manner has been partly uncovered. This review provides a global view of nuclear reassembly with a focus on the roles of dephosphorylation events. It also identifies important open questions and proposes hypotheses.

Mitotic exit requires the dephosphorylation of many proteins whose phosphorylation was needed for mitosis. Protein phosphatase 2A with its B55 regulatory subunit (PP2A-B55) promotes this transition. However, the events and substrates that it regulates are incompletely understood. We used proteomic approaches in Drosophila to identify proteins that interact with and are dephosphorylated by PP2A-B55. Among several candidates, we identified emerin (otefin in Drosophila ). Emerin resides in the inner nuclear membrane and interacts with the DNA-binding protein barrier-to-autointegration factor (BAF) via a LEM domain. We found that the phosphorylation of emerin at Ser50 and Ser54 near its LEM domain negatively regulates its association with BAF, lamin and additional emerin in mitosis. We show that dephosphorylation of emerin at these sites by PP2A-B55 determines the timing of nuclear envelope reformation. Genetic experiments indicate that this regulation is required during embryonic development. Phosphoregulation of the emerin–BAF complex formation by PP2A-B55 appears as a key event of mitotic exit that is likely conserved across species.