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bioRxiv · 10.64898/2026.01.23.701336

Kinetochore clustering is mediated by Mps1 phosphorylation of conserved MELT motifs in Stu1

Mallet, D. R.·Jiang, M.·Minnuto, G. M.·Biggins, S.
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Abstract

Unattached kinetochores promote microtubule capture while preventing cell cycle progression during mitosis. The Mps1 kinase controls these events by mediating kinetochore assembly of the fibrous corona in animal cells and by triggering the spindle checkpoint. In budding yeast, which does not assemble a fibrous corona, the Stu1 and Slk19 spindle proteins promote microtubule capture by clustering unattached kinetochores, but the underlying mechanism is unclear. Here, we show that Mps1 controls this pathway by phosphorylating two conserved MELT motifs in Stu1 to recruit Slk19 and mediate kinetochore clustering. Structural analysis of the Stu1:Slk19 complex reveals long, string-like filaments and offers mechanistic insight into how kinetochores might cluster. Our findings suggest the regulation of kinetochore capture is a conserved Mps1 function across eukaryotes. SUMMARYUnattached kinetochores cluster in budding yeast to promote microtubule capture. Mallett et al. dissect the molecular mechanisms of this pathway, showing Mps1 kinase regulates an interaction between Stu1 and Slk19 to drive clustering.

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Mallet, D. R., Jiang, M., Minnuto, G. M., Biggins, S.. 2026-01-25. Kinetochore clustering is mediated by Mps1 phosphorylation of conserved MELT motifs in Stu1. https://doi.org/10.64898/2026.01.23.701336

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