Mps1 and Ipl1/Aurora B Act Sequentially to Correctly Orient Chromosomes on the Meiotic Spindle of Budding Yeast

Abstract

The conserved kinases Mps1 and Ipl1/Aurora B are critical for enabling chromosomes to attach to microtubules such that partner chromosomes will be segregated correctly from each other, but the precise roles of these kinases have been unclear. Here, imaging of live yeast cells was performed to elucidate the stages of chromosome-microtubule interactions, and their regulation by Ipl1 and Mps1, through meiosis I. Ipl1 was found to release kinetochore-microtubule (kMT) associations following meiotic entry, liberating chromosomes to begin homologous pairing. Surprisingly, most chromosome pairs were found to begin their spindle interactions with incorrect kMT attachments. Ipl1 released these improper connections while Mps1 triggered the formation of new force-generating microtubule attachments. This microtubule release and reattachment cycle can prevent catastrophic chromosome segregation errors in meiosis.

Dual mechanisms prevent premature chromosome segregation during meiosis

“…During normal meiosis, following prophase exit, attachments of centromeres to the meiotic spindle typically result in poleward movement of the centromeres such that, in early metaphase, most centromeres are clustered at the poles ( Fig. 1A; Meyer et al 2013). We monitored attachment of chromosome I to precocious spindles by measuring the distance between CEN1 and the spindle pole.…”

“…To test this, we analyzed the interactions of chromosomes with the precocious spindles formed in ipl1 mutants. To avoid potential phenotypes from the loss of Ipl1 activity at earlier steps in meiosis (Meyer et al 2013), we allowed cells to proceed to pachytene with a functional version of Ipl1, Ipl1-as5, then inactivated this Ipl1-as5 (Pinsky et al 2006) by the addition of 1-NA-PP1 to the medium. Pachytene cells were first accumulated by blocking expression of NDT80 (Chu and Herskowitz 1998), and then Ipl1 was inhibited to allow precocious spindle formation.…”

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment

“…In budding yeast mitosis, Mps1 regulates mitotic chromosome alignment by promoting kinetochore biorientation independently of Ipl1 (aurora B in humans) (31), but in budding yeast meiosis Mps1 must collaborate with Ipl1 to mediate meiotic kinetochore biorientation (32). In humans, Mps1 regulates chromosomal alignment by modulating aurora B kinase activity (33), but recent chemical biology studies show that Mps1 kinase activity is important for proper chromosome alignment and segregation, independently of aurora B (22,(34)(35)(36).…”

From equator to pole: splitting chromosomes in mitosis and meiosis

“…In a manner similar to biorientation of sister chromatids in mitosis, tension and the action of Aurora B kinase play critical roles in achieving correct biorientation of homologs (Monje-Casas et al 2007;Sakuno et al 2011;Meyer et al 2013).…”