Spo13 prevents premature cohesin cleavage during meiosis

Abstract

Meiosis produces gametes through two successive nuclear divisions, meiosis I and meiosis II. In contrast to mitosis and meiosis II, where sister chromatids are segregated, during meiosis I, homologous chromosomes are segregated. This requires the monopolar attachment of sister kinetochores and the loss of cohesion from chromosome arms, but not centromeres, during meiosis I. The establishment of both sister kinetochore mono-orientation and cohesion protection rely on the budding yeast meiosis I-specific Spo13 protein, the functional homolog of fission yeast Moa1 and mouse MEIKIN. Here we investigate the effects of loss of SPO13 on cohesion during meiosis I. Unlike wild type, cells lacking SPO13 fail to maintain the meiosis-specific cohesin subunit, Rec8, at centromeres and segregate sister chromatids to opposite poles during anaphase I. We show that the cohesin-destabilizing factor, Wpl1, is not primarily responsible for the loss of cohesion during meiosis I. Instead, premature loss of centromeric cohesin during anaphase I in spo13Δ cells relies on separasedependent cohesin cleavage. Further, cohesin loss in spo13Δ anaphase I cells is blocked by forcibly tethering the regulatory subunit of protein phosphatase 2A, Rts1, to Rec8. Our findings indicate that separase-dependent cleavage of phosphorylated Rec8 causes premature cohesin loss in spo13Δ cells.

Loss of Sister Kinetochore Co-orientation and Peri-centromeric Cohesin Protection after Meiosis I Depends on Cleavage of Centromeric REC8

“…Indeed, our demonstration that SGOL2 can be inactivated through proteolytic cleavage during meiosis II without functional consequences is inconsistent with the suggestion that the dissipation of protection after meiosis I is mediated by the binding of a conserved histone chaperone SET/TAF-1b specifically at peri-centromeric region during meiosis II (Chambon et al, 2013; Wassmann, 2013). Spo13/Moa1/MEIKIN are meiosis-specific proteins from budding yeast, fission, and mammals that share the ability to bind to Polo-like kinases and have roles in both co-orientation of sister kinetochores and protection of cohesion (Galander et al, 2019; Katis et al, 2004a; Kim et al, 2015), raising the possibility that Spo13-like proteins may regulate the activity of centromeric cohesin.…”

“…Though not highly conserved in amino-acid sequences, all members of the family are expressed exclusively during meiosis and have the property of recruiting Polo-like kinases to kinetochores. Because their ablation compromises protection of peri-centromeric cohesion by Shugoshin/Mei-S332 proteins (Katis et al, 2004a; Klapholz & Esposito, 1980; Lee et al, 2004; Shonn et al, 2002) and regulation of the anaphase-promoting complex/cyclosome (APC/C) activity (Katis et al, 2004b) as well as co-orientation (Galander et al, 2019; Kim et al, 2015; Matos et al, 2008; Miyazaki et al, 2017), these Spo13-like proteins should be viewed as factors that regulate directly or indirectly numerous properties of meiotic centromeres.…”