A model for Scs2-Siz2–dependent mitotic SUMOylation at the INM and its role in chromatin recruitment. (A) Early in mitosis, Siz2 as well as telomeres and activated INO1 localize within the nucleoplasm. Progression through metaphase and into anaphase is accompanied by the phosphorylation of Siz2 that directs its interaction with the integral membrane protein Scs2 at the INM. (B) Siz2 phosphorylation facilitates Scs2-Siz2 association through the Scs2 MSP domain and an FFAT-like motif in Siz2. These interactions lead to Scs2 SUMOylation and the association of Scs2-SUMO with a SIM motif in Siz2, further stabilizing the Scs2–Siz2 complex. The Scs2–Siz2 SUMO ligase complex then directs the SUMOylation of INM-associated proteins, including Sir4 and proteins associated with the activated INO1 locus, and these modifications facilitate subtelomeric chromatin association with Sir4 at the INM and activated INO1 with an NPC. (C) As cells exit mitosis and undergo cytokinesis, dephosphorylation of Siz2 and Ulp1-dependent deSUMOylation of Scs2 and other proteins along the INM occurs. These events lead to the dissolution of the Scs2–Siz2 complex, while telomeres and activated INO1 remain associated with the nuclear periphery. ONM, outer nuclear membrane; Pi, inorganic phosphate; Su, SUMO.
