Reductional Meiosis I Chromosome Segregation Is Established by Coordination of Key Meiotic Kinases

Abstract

Summary Meiosis produces gametes through a specialized, two-step cell division, which is highly error prone in humans. Reductional meiosis I, where maternal and paternal chromosomes (homologs) segregate, is followed by equational meiosis II, where sister chromatids separate. Uniquely during meiosis I, sister kinetochores are monooriented and pericentromeric cohesin is protected. Here, we demonstrate that these key adaptations for reductional chromosome segregation are achieved through separable control of multiple kinases by the meiosis-I-specific budding yeast Spo13 protein. Recruitment of Polo kinase to kinetochores directs monoorientation, while independently, cohesin protection is achieved by containing the effects of cohesin kinases. Therefore, reductional chromosome segregation, the defining feature of meiosis, is established by multifaceted kinase control by a master regulator. The recent identification of Spo13 orthologs, fission yeast Moa1 and mouse MEIKIN, suggests that kinase coordination by a meiosis I regulator may be a general feature in the establishment of reductional chromosome segregation.

Meiosis I Kinase Regulators: Conserved Orchestrators of Reductional Chromosome Segregation

“…[ 9 ] Indeed, all four proteins carry a large number of serine and threonine residues (Figure 2B), which are targets for phosphorylation. Consistently, both Moa1 MOKIR[ 10 ] and Spo13 MOKIR[ 11,12 ] have been found to be phosphorylated.…”

“…[ 13,14 ] Indeed, Polo binding through the PBD‐binding domain of MOKIRs has been demonstrated in mouse, Drosophila , fission and budding yeasts, and abrogation of the Polo‐MOKIR interaction is detrimental for chromosome segregation in all cases. [ 11,12,15,16 ] In budding and fission yeasts, and mouse, MOKIRs recruit Polo kinase to kinetochores through the PBD‐binding region, whereas in Drosophila , this region is important for the sequestration of Polo on the spindle (Figure 2D). [ 11,12,15,16 ]…”

“…[ 11,12,15,16 ] In budding and fission yeasts, and mouse, MOKIRs recruit Polo kinase to kinetochores through the PBD‐binding region, whereas in Drosophila , this region is important for the sequestration of Polo on the spindle (Figure 2D). [ 11,12,15,16 ]…”

“…[ 26 ] Full Rec8 phosphorylation relies on PLK1 Polo in mice, [ 27 ] Cki1 in fission yeast, [ 28 ] and casein kinase 1δ (CK1δ), Dbf4‐dependent kinase (DDK) and Cdc5 Polo in budding yeast, [ 26,29 ] although the contribution of Cdc5 Polo to cleavage is under debate. [ 26,29,30 ] However, our recent data has shown that tethering of Cdc5 Polo directly to Rec8 in meiosis can promote loss of cohesion between sister chromatids at anaphase I, suggesting that Cdc5 Polo contributes to cohesin removal, [ 12 ] although whether it does so through promoting separase‐dependent Rec8 cleavage or via the cleavage‐independent, Wapl‐dependent cohesin removal pathway is unknown. In Drosophila , meiotic cohesin does not contain a Rec8‐like subunit.…”

“…[ 39,40 ] Shugoshins also bind to and localize with cohesin during meiosis. [ 12,41 ] Whether shugoshins also counteract Wapl during meiosis is not clear, but they are known to protect Rec8 from separase‐dependent cleavage in a multitude of organisms, thereby ensuring the maintenance of pericentromeric cohesion until meiosis II. [ 41–47 ] To achieve this, shugoshins recruit protein phosphatase 2A (PP2A; Table 1) to pericentromeres by binding of the PP2A B’ regulatory subunit.…”