UC San Diego

In metazoa, nuclear pore complexes (NPCs) assemble from disassembled precursors into a reforming nuclear envelope (NE) at the end of mitosis, and into growing intact NEs during interphase. Whether there are differences in the mechanism of NPC assembly in these two scenarios is a long standing question in the field that has not been addressed. Experiments described in this dissertation, show that ELYS, a nucleoporin critical for the recruitment of the essential Nup107/160 complex to chromatin, is crucial for NPC assembly at the end of mitosis, but is not required in interphase. Conversely, the transmembrane nucleoporin POM121 is critical for the incorporation of the Nup107/160 complex into new assembly sites specifically during interphase and plays a role in fusing the two leaflets of the NE. We show that in contrast to post-mitosis, where the Nup107/160 complex is targeted to chromatin via ELYS, during interphase this NPC sub-complex assembles at sites of forming pores. These results indicate that, in organisms with open mitosis, NPCs assemble by two distinct mechanisms to accommodate cell cycle-dependent differences in NE topology