Ipl1/Aurora Kinase Suppresses S-CDK-Driven Spindle Formation during Prophase I to Ensure Chromosome Integrity during Meiosis

Abstract

Cells coordinate spindle formation with DNA repair and morphological modifications to chromosomes prior to their segregation to prevent cell division with damaged chromosomes. Here we uncover a novel and unexpected role for Aurora kinase in preventing the formation of spindles by Clb5-CDK (S-CDK) during meiotic prophase I and when the DDR is active in budding yeast. This is critical since S-CDK is essential for replication during premeiotic S-phase as well as double-strand break induction that facilitates meiotic recombination and, ultimately, chromosome segregation. Furthermore, we find that depletion of Cdc5 polo kinase activity delays spindle formation in DDR-arrested cells and that ectopic expression of Cdc5 in prophase I enhances spindle formation, when Ipl1 is depleted. Our findings establish a new paradigm for Aurora kinase function in both negative and positive regulation of spindle dynamics.

Autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast

“…; Newnham et al . ), suggesting that the Aurora kinase‐dependent inhibition of meiosis progression is likely a general phenomenon, and that autophagy dysfunctions may affect this regulation. We additionally observed aberrant intracellular localization of Clp1 phosphatase, which also regulates the cell cycle (Esteban et al .…”

“…Observation that Ark1 down-regulation in autophagy-defective mutants decreased or eliminated the delay of initiation of meiosis I and II indicates that meiosis progression may also be inhibited by Aurora kinase. Inhibition of meiosis I spindle formation by Aurora kinase has been reported in S. cerevisiae (Kim et al 2013;Newnham et al 2013), suggesting that the Aurora kinase-dependent inhibition of meiosis progression is likely a general phenomenon, and that autophagy dysfunctions may affect this regulation. We additionally observed aberrant intracellular localization of Clp1 phosphatase, which also regulates the cell cycle (Esteban et al 2004;Wolfe & Gould 2004) and may contribute to the meiosis cessation or delay.…”

Aurora B and C kinases regulate prophase exit and chromosome segregation during spermatogenesis

“…In sum, our data demonstrate that chromosome restructuring events at the axis, and more generally throughout the chromatin, must be coordinated with cell-cycle progression to restrict spermatocytes from entering metaphase I prior to SC disassembly. The budding yeast AURK, Ipl1, blocks cell cycle progression during early meiotic prophase by suppressing S-CDK activity (Newnham et al, 2013). In the context of depleted Ipl1, spindle pole body maturation and 2 4 5 separation, as well as cell cycle progression are decoupled and cells erroneously progress to metaphase with linear stretches of SC components still present at the axis (Jordan et al, 2009;Newnham et al, 2013).…”

“…The budding yeast AURK, Ipl1, blocks cell cycle progression during early meiotic prophase by suppressing S-CDK activity (Newnham et al, 2013). In the context of depleted Ipl1, spindle pole body maturation and 2 4 5 separation, as well as cell cycle progression are decoupled and cells erroneously progress to metaphase with linear stretches of SC components still present at the axis (Jordan et al, 2009;Newnham et al, 2013). However, mammals express three AURK proteins, where AURKA appears to predominantly function in the cytoplasm during centrosome maturation, and AURKB/C are required for the chromosomal events which take place during the G2/MI transition 2 5 0 in males.…”

“…7 0 Aurora kinases (AURKs) are implicated in regulating SC dynamics during meiosis. In budding yeast there is a single AURK, Ipl1, which promotes efficiency of SC disassembly and integrates chromosome restructuring events with cell cycle progression (Jordan et al, 2009;Newnham et al, 2013). Mammalian spermatocytes, however, express three AURK paralogs (AURKA, B, and 7 5 C) (Tang et al, 2006).…”