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STAG3‐mediated stabilization of REC8 cohesin complexes promotes chromosome synapsis during meiosis

Tomoyuki Fukuda, Nanaho Fukuda, Ana Agostinho, Abrahan Hernández‐Hernández, Anna Kouznetsova, Christer Höög

Author Affiliations

  1. Tomoyuki Fukuda*,1,2,
  2. Nanaho Fukuda2,
  3. Ana Agostinho2,
  4. Abrahan Hernández‐Hernández2,
  5. Anna Kouznetsova2 and
  6. Christer Höög*,2
  1. 1Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan
  2. 2Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
  1. * Corresponding author. Tel: +81 743725543; Fax: +81 743725549; E‐mail: tfukuda{at}bs.naist.jp

    Corresponding author. Tel: +46 852487365; Fax: +46 8323672; E‐mail: christer.hoog{at}ki.se

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Abstract

Cohesion between sister chromatids in mitotic and meiotic cells is promoted by a ring‐shaped protein structure, the cohesin complex. The cohesin core complex is composed of four subunits, including two structural maintenance of chromosome (SMC) proteins, one α‐kleisin protein, and one SA protein. Meiotic cells express both mitotic and meiosis‐specific cohesin core subunits, generating cohesin complexes with different subunit composition and possibly separate meiotic functions. Here, we have analyzed the in vivo function of STAG3, a vertebrate meiosis‐specific SA protein. Mice with a hypomorphic allele of Stag3, which display a severely reduced level of STAG3, are viable but infertile. We show that meiocytes in homozygous mutant Stag3 mice display chromosome axis compaction, aberrant synapsis, impaired recombination and developmental arrest. We find that the three different α‐kleisins present in meiotic cells show different dosage‐dependent requirements for STAG3 and that STAG3‐REC8 cohesin complexes have a critical role in supporting meiotic chromosome structure and functions.

See also: T Winters et al (June 2014)

Synopsis

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Distinct cohesin complexes appear to mediate specialized chromosome organization function during meiosis. Analysis of a hypomorphic allele of one meiosis‐specific cohesin subunit, STAG3/SA3, reveals its essential function in promoting chromosome synapsis during mouse meiosis.

  • STAG3 is an essential subunit of the meiotic cohesin complex, required for gametogenesis and fertility.

  • The three different α‐kleisin subunits of the cohesin complex show different dosage‐dependent requirements for STAG3.

  • STAG3‐REC8 containing cohesin complexes contribute to chromosome axis organization, chromosome synapsis, and recombination in meiotic cells.

The EMBO Journal (2014) 33: 1243–1255

  • Received November 5, 2013.
  • Revision received March 26, 2014.
  • Accepted March 28, 2014.
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