Condensin II activation by M18BP1

Alessandro Borsellini; Duccio Conti; Erin Cutts; Rebecca J. Harris; Kai Walstein; Andrea Graziadei; Valentina Cecatiello; Tom F. Aarts; Ren Xie; Abdelghani Mazouzi; Sushweta Sen; Claire Hoencamp; Richard Pleuger; Sabrina Ghetti; Lina Oberste-Lehn; Dongqing Pan; Tanja Bange; Judith H.I. Haarhuis; Anastassis Perrakis A; Thijn R. Brummelkamp; Benjamin D. Rowland; Andrea Musacchio; Alessandro Vannini

doi:10.1016/j.molcel.2025.06.014

Cell BiologyMolecular CellJul 1, 2025

Peer-reviewed journal article

Condensin II activation by M18BP1

Alessandro Borsellini iD, Duccio Conti, Erin Cutts iD, Rebecca J. Harris iD, Kai Walstein iD, Andrea Graziadei iD, Valentina Cecatiello iD, Tom F. Aarts, Ren Xie iD, Abdelghani Mazouzi iD, Sushweta Sen, Claire Hoencamp iD, Richard Pleuger iD, Sabrina Ghetti iD, Lina Oberste-Lehn iD, Dongqing Pan iD, Tanja Bange iD, Judith H.I. Haarhuis, Anastassis Perrakis A iD, Thijn R. Brummelkamp iD, Benjamin D. Rowland iD, Andrea Musacchio iD, Alessandro Vannini iD

Abstract

Condensin complexes promote the drastic spatial rearrangement of the genome upon mitotic entry. Condensin II initiates chromosome condensation in early mitosis. To prevent chromosome condensation during interphase, condensin II is inhibited by MCPH1, but the mechanism is 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. M18BP1 directly binds condensin IIs CAP-G2 subunit and competes with MCPH1 for binding. Upon mitotic entry, CDK1 mediated phosphorylation may promote a switch from MCPH1 to M18BP1 binding to activate condensin II. Our results identify a fundamental and evolutionarily conserved mechanism of condensin II activation.

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