Spo13 prevents premature cohesin cleavage during meiosis

Abstract

Background: 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. Methods: Here we investigate the effects of loss of SPO13 on cohesion during meiosis I using a live-cell imaging approach. Results: 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 separase-dependent 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. Conclusions: Our findings indicate that separase-dependent cleavage of phosphorylated Rec8 causes premature cohesin loss in spo13Δ cells.

Eco1-dependent cohesin acetylation anchors chromatin loops and cohesion to define functional meiotic chromosome domains

“…However, ChIP-qPCR revealed that both Sgo1 and Spo13 localize to chromosomes in eco1- aa cells ( Figure 8—figure supplement 2 ). Both proteins follow a similar pattern to Rec8, showing reduced chromosomal association in eco1-aa cells that is rescued by WPL1 deletion ( Figure 8—figure supplement 2 ), consistent with a requirement for cohesin for the chromosomal association of Sgo1 and Spo13 ( Galander et al, 2019b ; Kiburz et al, 2005 ). Therefore, a failure in cohesin protection is unlikely to be the cause of meiosis II missegregation in eco1-aa cells.…”

“…Therefore, Eco1 is essential for chromosome segregation during meiosis II, even in the absence of Wpl1. One potential explanation for these findings is that localization of the cohesin protector protein, shugoshin (Sgo1), or the meiotic protein Spo13, which is also required for cohesin protection during meiosis I ( Galander et al, 2019b ; Galander et al, 2019a ; Katis et al, 2004 ; Lee et al, 2004 ), may require Smc3 acetylation. However, ChIP-qPCR revealed that both Sgo1 and Spo13 localize to chromosomes in eco1- aa cells ( Figure 8—figure supplement 2 ).…”

“…For calibrated ChIP-seq (Smc3), we used the method of Hu et al, 2015 , as modified by Galander et al, 2019b . For each condition, 200 ml of S. cerevisiae meiotic culture was grown and fixed as for ChIP-qPCR and frozen in four pellets (each from 50 ml culture).…”

The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint

“…In line with this possibility, it has been shown that overexpression of CDC5 from the CUP1 promoter during meiosis leads to reduced electrophoretic mobility and premature degradation of Spo13 [48]. Spo13 is a critical regulator of centromeric cohesion and it is required for proper chromosome segregation at meiosis I [49]; in fact, SPO13deficient cells undergo a single round of meiotic nuclear division and generate dyads [50]. The reduced spore viability and impaired formation of asci containing 4 spores observed in the cdc5-ΔN70 mutant (Figure 3) may be a consequence of altered Spo13 and/or cohesin function.…”

Trisomy 21 and Assisted Reproductive Technologies: A review

“…However, there is evidence that links the development of aneuploidies to advanced maternal age: recombination errors that occur during the fetal development of the mother, age-related accumulation of damaged DNA, cohesin degradation during dictyate that can lead to the premature loss of chromosomes or sister chromatids ( Duncan et al ., 2012 ) and alterations in the SAC during the spindle formation process, inevitably leading to the delay of cell division ( Hauf & Watanabe, 2004 ; Tanaka, 2005 ; Touati & Wassmann, 2016 ). A weakened SAC would lead to the premature onset of anaphase prior to chromosomal attachment to the spindle microtubules, thus leading to potential errors in chromosome segregation ( Galander et al ., 2019 ). Likewise, it has been demonstrated that aging also has a negative effect in the concentration of cohesion and inhibin proteins, which are part of the SAC, and play a key role in normal cell division patterns ( Duncan et al ., 2012 ; Nabti et al ., 2017 ).…”