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25.04.2025 - 10:15:10
The Spc105/Kre28 complex promotes mitotic error correction by outer kinetochore recruitment of Ipl1/Sli15
Eukaryotic cells segregate chromosomes with remarkable precision in order to avoid aneuploidies and genomic instability. The conserved protein kinase Aurora B has emerged as the key regulator of kinetochore-microtubule interactions. In prometaphase of mitosis its activity is required to destabilize kinetochore-microtubule interactions that would lead to mis-segregation, a crucial process termed error correction. The molecular mechanisms that allow Aurora B to differentiate between incorrect and correct attachments, however, remain to be established. New results from the Westermann lab (A01) just published in the EMBO Journal (Dudziak et al. 2025) provide important new insights into this process. Combining genetic and biochemical experiments in the model system budding yeast, they show that a conserved protein complex of the outer kinetochore Spc105/Kre28 (Knl1/Zwint in humans), provides a binding site for the Ipl1 (Aurora B) activator protein Sli15 (INCENP). Recruitment of a short Sli15 motif to Spc105 is crucially required for tension-sensitive error correction in yeast cells. These finding bring us an important step closer towards understanding how kinetochores act as force-sensitive signaling scaffolds during sister chromatid biorientation
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