SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes

Development. 2017 May 1;144(9):1648-1660. doi: 10.1242/dev.145607. Epub 2017 Mar 16.


SMC complexes include three major classes: cohesin, condensin and SMC5/6. However, the localization pattern and genetic requirements for the SMC5/6 complex during mammalian oogenesis have not previously been examined. In mouse oocytes, the SMC5/6 complex is enriched at the pericentromeric heterochromatin, and also localizes along chromosome arms during meiosis. The infertility phenotypes of females with a Zp3-Cre-driven conditional knockout (cKO) of Smc5 demonstrated that maternally expressed SMC5 protein is essential for early embryogenesis. Interestingly, protein levels of SMC5/6 complex components in oocytes decline as wild-type females age. When SMC5/6 complexes were completely absent in oocytes during meiotic resumption, homologous chromosomes failed to segregate accurately during meiosis I. Despite what appears to be an inability to resolve concatenation between chromosomes during meiosis, localization of topoisomerase IIα to bivalents was not affected; however, localization of condensin along the chromosome axes was perturbed. Taken together, these data demonstrate that the SMC5/6 complex is essential for the formation of segregation-competent bivalents during meiosis I, and findings suggest that age-dependent depletion of the SMC5/6 complex in oocytes could contribute to increased incidence of oocyte aneuploidy and spontaneous abortion in aging females.

Keywords: Aneuploidy; Chromosome segregation; Cohesin; Condensin; Meiosis; SMC5/6.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Aging / physiology
  • Aneuploidy
  • Animals
  • Blastocyst / cytology
  • Blastocyst / metabolism
  • Cell Cycle Proteins / metabolism*
  • Chromosome Segregation*
  • Chromosomes, Mammalian / metabolism*
  • DNA-Binding Proteins / metabolism
  • Female
  • Fertilization in Vitro
  • Genotyping Techniques
  • Heterochromatin / metabolism
  • Infertility, Female
  • Integrases / metabolism
  • Male
  • Maternal Inheritance / genetics
  • Meiosis*
  • Metaphase
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Multiprotein Complexes / metabolism
  • Mutation / genetics
  • Oocytes / cytology*
  • Oocytes / metabolism*
  • Sexual Behavior, Animal


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Heterochromatin
  • Multiprotein Complexes
  • SMC5 protein, mouse
  • SMC6 protein, mouse
  • condensin complexes
  • Cre recombinase
  • Integrases
  • Adenosine Triphosphatases