Smc1β is required for activation of SAC during mouse oocyte meiosis

Cell Cycle. 2017 Mar 19;16(6):536-544. doi: 10.1080/15384101.2017.1282583. Epub 2017 Jan 24.

Abstract

Smc1β is a meiosis-specific cohesin subunit that is essential for sister chromatid cohesion and DNA recombination. Previous studies have shown that Smc1β-deficient mice in both sexes are sterile. Ablation of Smc1β during male meiosis leads to the blockage of spermatogenesis in pachytene stage, and ablation of Smc1β during female meiosis generates a highly error-prone oocyte although it could develop to metaphase II stage. However, the underlying mechanisms regarding how Smc1β maintains the correct meiotic progression in mouse oocytes have not been clearly defined. Here, we find that GFP-fused Smc1β is expressed and localized to the chromosomes from GV to MII stages during mouse oocyte meiotic maturation. Knockdown of Smc1β by microinjection of gene-specific morpholino causes the impaired spindle apparatus and chromosome alignment which are highly correlated with the defective kinetochore-microtubule attachments, consequently resulting in a prominently higher incidence of aneuploid eggs. In addition, the premature extrusion of polar bodies and escape of metaphase I arrest induced by low dose of nocodazole treatment in Smc1β-depleted oocytes indicates that Smc1β is essential for activation of spindle assembly checkpoint (SAC) activity. Collectively, we identify a novel function of Smc1β as a SAC participant beyond its role in chromosome cohesion during mouse oocyte meiosis.

Keywords: SAC; Smc1β; aneuploid egg; chromosome alignment; kinetochore-microtubule attachment; spindle assembly.

MeSH terms

  • Aneuploidy
  • Animals
  • Cell Cycle Proteins / metabolism*
  • Chromosomes, Mammalian / metabolism
  • Female
  • Gene Deletion
  • Gene Knockdown Techniques
  • Kinetochores / metabolism
  • M Phase Cell Cycle Checkpoints*
  • Meiosis*
  • Mice, Inbred ICR
  • Microtubules / metabolism
  • Oocytes / cytology*
  • Oocytes / metabolism*
  • Protein Transport

Substances

  • Cell Cycle Proteins
  • Smc1l2 protein, mouse