During interphase, chromosomes are surrounded by the nuclear envelope. The centrosomes that nucleate the mitotic spindle are located in the cytoplasm. For chromosomes to interact with the microtubules nucleated by the centrosomes, the nuclear envelope needs to be dismantled.

The nuclear envelope is a double-membrane extension of the endoplasmic reticulum containing many nuclear pore complexes (see Figures 1-12, 13-33, and 1-15). The lipid bilayer of the inner nuclear membrane is associated with the nuclear lamina, a meshwork of lamin filaments adjacent to the inside face of the nuclear envelope (Figure 19-19; see also Figure 1-15). The three nuclear lamins (A, B, and C) present in vertebrate cells belong to a class of cytoskeletal proteins, the intermediate filaments, that are critical in supporting cellular membranes. Once mitotic CDKs are activated at the end of G₂, they phosphorylate specific serine residues in all three nuclear lamins. This phosphorylation causes depolymerization of the lamin intermediate filaments. Depolymerization of the nuclear lamins leads to disintegration of the nuclear lamina and contributes to disassembly of the nuclear envelope.

Mitotic CDKs also affect other nuclear envelope components. The CDKs phosphorylate specific nucleoporins, which causes nuclear pore complexes to dissociate into subcomplexes during prophase. Phosphorylation of integral membrane proteins of the inner nuclear membrane is thought to decrease their affinity for chromatin and further contributes to the disassembly of the nuclear envelope. The weakening of the associations between the inner nuclear membrane proteins and the nuclear lamina and chromatin allows sheets of inner nuclear membrane to retract into the endoplasmic reticulum, which is continuous with the outer nuclear membrane.