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CDK activity at the centrosome regulates the cell cycle.

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posted on 2024-04-09, 08:39 authored by Emma L Roberts, Jessica Greenwood, Nitin Kapadia, Tania Auchynnikava, Souradeep Basu, Paul Nurse
In human cells and yeast, an intact "hydrophobic patch" substrate docking site is needed for mitotic cyclin centrosomal localization. A hydrophobic patch mutant (HPM) of the fission yeast mitotic cyclin Cdc13 cannot enter mitosis, but whether this is due to defective centrosomal localization or defective cyclin-substrate docking more widely is unknown. Here, we show that artificially restoring Cdc13-HPM centrosomal localization promotes mitotic entry and increases CDK (cyclin-dependent kinase) substrate phosphorylation at the centrosome and in the cytoplasm. We also show that the S-phase B-cyclin hydrophobic patch is required for centrosomal localization but not for S phase. We propose that the hydrophobic patch is essential for mitosis due to its requirement for the local concentration of cyclin-CDK with CDK substrates and regulators at the centrosome. Our findings emphasize the central importance of the centrosome as a hub coordinating cell-cycle control and explain why the cyclin hydrophobic patch is essential for mitosis.

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Crick (Grant ID: CC2003, Grant title: Nurse CC2003) Wellcome Trust (Grant ID: 214183/Z/18/Z, Grant title: WT 214183/Z/18/Z) Wellcome Trust (Grant ID: 093917/C/10/A, Grant title: WT 093917/C/10/A) Crick (Grant ID: CC1063, Grant title: STP Proteomics)

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