Proteomics

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Condensin II Activation by the centromeric protein M18BP1


ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

DISEASE(S): Disease Free

SUBMITTER: Andrea Graziadei  

LAB HEAD: Andrea Graziadei

PROVIDER: PXD051886 | Pride | 2025-07-09

REPOSITORIES: Pride

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Publications


Condensin I and II promote the drastic spatial rearrangement of the human genome upon mitotic entry. While condensin II is known to initiate this process in early mitosis, what triggers its activation and loading onto chromatin at this juncture remains unclear. Through genetic and proteomic approaches, we identify MIS18-binding protein 1 (M18BP1), a protein required to maintain centromere identity, as the elusive factor required for condensin II localization to chromatin. M18BP1 directly binds c  ...[more]

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