M18BP1 is a determinant of Condensin II activation

Condensin I and Condensin II promote drastic spatial compaction (condensation) of the genome upon mitotic entry. Condensin I binds chromatin only after dissolution of the nuclear envelope in prophase. Conversely, Condensin II is nuclear throughout the cell cycle and initiates chromosome condensation. Previous studies demonstrated that MCPH1 inhibits Condensin II to prevent chromosome condensation during interphase. Mechanisms that promote Condensin II activation in early mitosis likely exist but are currently unknown. Through genetic and proteomic approaches, we identify M18BP1, a protein previously associated with centromere identity, as a factor required for Condensin II localization to chromatin during mitosis. To activate and localize Condensin II, M18BP1 directly binds the CAP-G2 subunit. M18BP1 and MCPH1 compete for CAP-G2 binding, and CDK1 phosphorylation promotes replacement of MCPH1 with M18BP1 to activate Condensin II upon mitotic entry. Our results identify a fundamental and evolutionarily conserved mechanism of Condensin II activation