Killing two birds with one stone: how budding yeast Mps1 controls chromosome segregation and spindle assembly checkpoint
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MINI-REVIEW
Killing two birds with one stone: how budding yeast Mps1 controls chromosome segregation and spindle assembly checkpoint through phosphorylation of a single kinetochore protein Giorgia Benzi1 · Simonetta Piatti1 Received: 9 June 2020 / Revised: 23 June 2020 / Accepted: 25 June 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract During mitosis, the identical sister chromatids of each chromosome must attach through their kinetochores to microtubules emanating from opposite spindle poles. This process, referred to as chromosome biorientation, is essential for equal partitioning of the genetic information to the two daughter cells. Defects in chromosome biorientation can give rise to aneuploidy, a hallmark of cancer and genetic diseases. A conserved surveillance mechanism called spindle assembly checkpoint (SAC) prevents the onset of anaphase until biorientation is attained. Key to chromosome biorientation is an error correction mechanism that allows kinetochores to establish proper bipolar attachments by disengaging faulty kinetochore–microtubule connections. Error correction relies on the Aurora B and Mps1 kinases that also promote SAC signaling, raising the possibility that they are part of a single sensory device responding to improper attachments and concomitantly controlling both their disengagement and a temporary mitotic arrest. In budding yeast, Aurora B and Mps1 promote error correction independently from one another, but while the substrates of Aurora B in this process are at least partially known, the mechanism underlying the involvement of Mps1 in the error correction pathway is unknown. Through the characterization of a novel mps1 mutant and an unbiased genetic screen for extragenic suppressors, we recently gained evidence that a common mechanism based on Mps1-dependent phosphorylation of the Knl1/Spc105 kinetochore scaffold and subsequent recruitment of the Bub1 kinase is critical for the function of Mps1 in chromosome biorientation as well as for SAC activation (Benzi et al. EMBO Rep, 2020). Keywords Mitosis · Chromosome biorientation · Spindle assembly checkpoint · Kinetochore · Mps1 · Aurora B
Introduction Chromosome segregation is a vulnerable, error-prone process that must be tightly regulated in time and space. Several requirements must be fulfilled for daughter cells to get an equal chromosome complement. First, chromosomes must be faithfully duplicated into identical sister chromatids through DNA replication. Second, sister chromatids must be glued together by sister chromatid cohesion, which allows cells to distinguish genetically identical from distinct chromosomes. Third, sister chromatids need to attach via their kinetochores to microtubules emanating from opposite Communicated by M. Kupiec. * Simonetta Piatti [email protected] 1
CRBM, University of Montpellier, CNRS, 1919 Route de Mende, 34293 Montpellier, France
spindle poles, a process referred to as chromosome biorientation (reviewed in Bloom and Yeh 2010). If this fails, a surveill
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