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bioRxiv · 10.1101/2024.04.13.589357

KIF2C-induced nuclear condensation concentrates PLK1 and phosphorylated BRCA2 at the kinetochore microtubules in mitosis

Skobelkina, A.·Julien, M.·Jeannin, S.·Miron, S.·Egger, T.·Chaaban, R.·Bouvignies, G.·Ghouil, R.·Friel, C.·BUSSO, D.·Theillet, F.-X.·Le Bars, R.·Carreira, A.·Constantinou, A.·Basbous, J.·ZINN-JUSTIN, S.
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Abstract

During mitosis, the human microtubule depolymerase KIF2C increases the turnover of kinetochore-microtubule attachments. This facilitates the correction of attachment errors. Moreover, BRCA2 phosphorylated at Thr207 by PLK1 (BRCA2-pT207) assembles a complex including PLK1, PP2A and BUBR1 that contributes to the stability of the kinetochore-microtubule attachments. PLK1, together with Aurora B, critically regulate the accurate segregation of chromosomes. Here we demonstrate that KIF2C contains an N-terminal domain that binds directly to several phosphorylated peptides, including BRCA2-pT207. Using an optogenetic platform, we reveal that KIF2C assembles into membrane-less compartments or biomolecular condensates that are located next to microtubules. We provide evidence that condensate assembly depends on the presence of the newly defined N-terminal phospho-binding domain of KIF2C and on the kinase activities of Aurora B and PLK1. Moreover, KIF2C condensates concentrate active PLK1 and colocalize with BRCA2-pT207. We propose that, because of its phospho-dependent binding and oligomerization capacities, KIF2C forms biomolecular condensates that partition PLK1 and locally amplify its kinase activity during mitosis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/589357v1_ufig1.gif" ALT="Figure 1"> View larger version (80K): org.highwire.dtl.DTLVardef@3ff5bforg.highwire.dtl.DTLVardef@11efbdcorg.highwire.dtl.DTLVardef@1295118org.highwire.dtl.DTLVardef@18b3dd3_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Skobelkina, A., Julien, M., Jeannin, S., Miron, S., Egger, T., Chaaban, R., Bouvignies, G., Ghouil, R., Friel, C., BUSSO, D., Theillet, F.-X., Le Bars, R., Carreira, A., Constantinou, A., Basbous, J., ZINN-JUSTIN, S.. 2024-04-14. KIF2C-induced nuclear condensation concentrates PLK1 and phosphorylated BRCA2 at the kinetochore microtubules in mitosis. https://doi.org/10.1101/2024.04.13.589357

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