Abstract
Correct bioriented attachment of sister chromatids to the mitotic spindle is essential for chromosome segregation. In budding yeast, the conserved protein shugoshin (Sgo1) contributes to biorientation by recruiting the protein phosphatase PP2A-Rts1 and the condensin complex to centromeres. Using peptide prints, we identified a Serine-Rich Motif (SRM) of Sgo1 that mediates the interaction with condensin and is essential for centromeric condensin recruitment and the establishment of biorientation. We show that the interaction is regulated via phosphorylation within the SRM and we determined the phospho-sites using mass spectrometry. Analysis of the phosphomimic and phosphoresistant mutants revealed that SRM phosphorylation disrupts the shugoshin–condensin interaction. We present evidence that Mps1, a central kinase in the spindle assembly checkpoint, directly phosphorylates Sgo1 within the SRM to regulate the interaction with condensin and thereby condensin localization to centromeres. Our findings identify novel mechanisms that control shugoshin activity at the centromere in budding yeast.
Highlights
Biorientation of sister chromatids relies on two major processes
Proper chromosome segregation in eukaryotes is ensured through correct attachment of the spindle microtubules to the centromeric chromosomal regions
This enables the establishment of bioirentation, when each sister chromatid is attached to microtubules emanating from opposite spindle poles
Summary
Biorientation of sister chromatids relies on two major processes. First, spindle and kinetochore geometry facilitates the capture of sister kinetochores (KT) by microtubules (MTs) emanating from the opposite spindle poles [1,2]. Several proteins, whose activity must be tightly regulated and coordinated, are required for these processes Among these proteins are so-called shugoshins, a family of proteins containing two conserved domains with an important function in establishment of biorientation in mitosis and meiosis [5]. Shugoshins prevent cohesion loss at the centromere during mammalian mitosis, via a distinct mechanism that affects the prophase pathway [7]. These activities are carried out through the recruitment of a protein phosphatase 2A (PP2A-Rts in budding yeast, PP2A-B56 in mammalian cells) that reduces cohesin removal via its dephosphorylation [8]. The activity of shugoshins thereby facilitates centromeric conformation, establishment of biorientation, tension sensing and correction of aberrant MT-KT attachments
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