Shugoshin Is Essential for Meiotic Prophase Checkpoints in C. elegans

Abstract

Summary The conserved factor Shugoshin is dispensable in C. elegans for the two-step loss of sister chromatid cohesion that directs the proper segregation of meiotic chromosomes. We show that the C. elegans ortholog of Shugoshin, SGO-1, is required for checkpoint activity in meiotic prophase. This role in checkpoint function is similar to that of conserved proteins that structure meiotic chromosome axes. Indeed, null sgo-1 mutants exhibit additional phenotypes similar to that of a partial loss of function allele of the axis component, HTP-3: premature synaptonemal complex disassembly, the activation of alternate DNA repair pathways and an inability to recruit a conserved effector of the DNA damage pathway, HUS-1. SGO-1 localizes to pre-meiotic nuclei when HTP-3 is present but not yet loaded onto chromosome axes and genetically interacts with a central component of the cohesin complex, SMC-3, suggesting that it contributes to meiotic chromosome metabolism early in meiosis by regulating cohesin. We propose that SGO-1 acts during pre-meiotic replication to ensure fully functional meiotic chromosome architecture, rendering these chromosomes competent for checkpoint activity and normal progression of meiotic recombination. Given that most research on Shugoshin has focused on its regulation of sister chromatid cohesion during chromosome segregation, this novel role may be conserved but previously uncharacterized in other organisms. Further, our findings expand the repertoire of Shugoshin’s functions beyond coordinating regulatory activities at the centromere.

Shugoshin protects centromere pairing and promotes segregation of nonexchange partner chromosomes in meiosis

“…These experiments show that shugoshin is not needed for the establishment of centromere pairing, that centromere pairing dissolves after pachytene exit, and that shugoshin slows the dissolution of centromere pairing. In both nematodes and rice, SCs disassemble prematurely in the absence of shugoshin (30, 34). Thus, it could be that the protection of SC components at centromeres, observed in our studies, reflects a more general conserved role for shugoshins in modulating SC stability and the timing of its disassembly.…”

“…In yeasts and mouse oocytes, shugoshin recruits PP2A phosphatase to centromeres, rendering the centromeric cohesin refractory to cleavage by the protease separase at the metaphase I to anaphase I transition (25–29). Shugoshins also interact with other proteins (Mad2, MCAK, the chromosome passenger complex, and cohesin subunits) to modulate chromosome structure and segregation in meiosis and mitosis (27, 30–34). In budding and fission yeast, shugoshin acts by protecting the Rec8 component of cohesin from phosphorylation by casein kinase and also in budding yeast by the Dbf4 kinase (DDK).…”

Fission Yeast Methylenetetrahydrofolate Reductase Ensures Mitotic and Meiotic Chromosome Segregation Fidelity

“…On the other hand, it is also possible that Sgo1 and Rec8 may have roles that are functionally distinct from that of sister chromatid cohesion that is regulated in conjunction with heterochromatin during meiotic chromosome segregation. In fact, Shugoshin was reported to regulate meiotic prophase checkpoint in worm [ 36 ] and promote kinetochore microtubule stability [ 37 ]. Rec8 plays additional role to organize meiotic chromosome organization and modulate chromosomal compaction [ 38 , 39 ].…”

Shugoshin promotes efficient activation of spindle assembly checkpoint and timely spindle disassembly

“…Till date, among the species, shugoshin has been found on the chromatin at the centromeres/pericentromeres (Kitajima et al 2004, Kiburz et al 2005 and in the vicinity of telomeres (Vanoosthuyse et al 2007, Tashiro et al 2016. Its association with the chromosomal arms cannot be ruled out given its function on arm condensation in budding yeast (Kruitwagen et al 2018) and in the prophase checkpoint in C. elegans (Bohr et al 2018).…”

“…Recently, Sgo1 has been implicated in chromosomal arm condensation in S. cerevisiae indicating possible localization of ScSgo1 along the arms (Kruitwagen et al 2018). In C. elegans, shugoshin has been shown to be essential for meiotic prophase checkpoint perhaps through its interaction with cohesin along the chromosomes (Bohr et al 2018). In S. pombe, shugoshin relocalizes from centromeres to the vicinity of telomeres possibly to regulate subtelomeric gene repression and late firing of replication origins (Tashiro et al 2016).…”