Abstract
Centrosomes organize microtubules and are essential for spindle formation and chromosome segregation during cell division. Duplicated centrosomes are physically linked, but how this linkage is dissolved remains unclear. Yeast centrosomes are tethered by a nuclear-envelope-attached structure called the half-bridge, whose components have mammalian homologues. We report here that cleavage of the half-bridge protein Mps3 promotes accurate centrosome disjunction in budding yeast. Mps3 is a single-pass SUN-domain protein anchored at the inner nuclear membrane and concentrated at the nuclear side of the half-bridge. Using the unique feature in yeast meiosis that centrosomes are linked for hours before their separation, we have revealed that Mps3 is cleaved at its nucleus-localized N-terminal domain, the process of which is regulated by its phosphorylation at serine 70. Cleavage of Mps3 takes place at the yeast centrosome and requires proteasome activity. We show that noncleavable Mps3 (Mps3-nc) inhibits centrosome separation during yeast meiosis. In addition, overexpression of mps3-nc in vegetative yeast cells also inhibits centrosome separation and is lethal. Our findings provide a genetic mechanism for the regulation of SUN-domain protein-mediated activities, including centrosome separation, by irreversible protein cleavage at the nuclear periphery.
Highlights
Centrosomes nucleate microtubules and form a bipolar spindle that separates chromosomes during cell division
Mps3 cleavage promotes centrosome separation centrosome, is phosphorylated and subject to proteolytic cleavage in order to properly split the centrosomes before spindle formation and chromosome segregation
Understanding how SUN-domain proteins are posttranslationally modified can shed light on the regulation of centrosome separation; it provides insight into the homeostasis of SUNdomain proteins that are associated with many human diseases of the nuclear envelope
Summary
Centrosomes nucleate microtubules and form a bipolar spindle that separates chromosomes during cell division. Like DNA replication, centrosome duplication occurs only once per cell cycle. Duplicated centrosomes are tethered, and their timely separation ensures accurate chromosome segregation. Supernumerary centrosomes and the subsequent formation of aberrant spindles can lead to aneuploidy in humans [1, 2]. At the core of the animal centrosome lies a pair of centrioles, whose cleavage by the cysteine protease, separase, necessitates their disengagement [3], the substrate of the separase at the centriole remains controversial. How the centrosome linkage is dissolved is less clear. In particular whether irreversible protein cleavage is required for centrosome separation, called centrosome disjunction in animal cells, is not known
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