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Curr Biol. 2018 Oct 22;28(20):3199-3211.e3. doi: 10.1016/j.cub.2018.08.026. Epub 2018 Oct 4.

Shugoshin Is Essential for Meiotic Prophase Checkpoints in C. elegans.

Author information

1
Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
2
Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA. Electronic address: nbhalla@ucsc.edu.

Abstract

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.

KEYWORDS:

DNA damage response; HORMADs; checkpoint; chromosome axis; cohesin; homologous chromosome; meiosis; recombination; synapsis

PMID:
30293721
PMCID:
PMC6200582
[Available on 2019-10-22]
DOI:
10.1016/j.cub.2018.08.026

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