The cohesin complex is essential for mitosis and meiosis. The specific meiotic roles of individual cohesin proteins are incompletely understood. We report in vivo functions of the only meiosis-specific STAG component of cohesin, STAG3. Newly generated STAG3-deficient mice of both sexes are sterile with meiotic arrest. In these mice, meiotic chromosome architecture is severely disrupted as no bona fide axial elements (AE) form and homologous chromosomes do not synapse. Axial element protein SYCP3 forms dot-like structures, many partially overlapping with centromeres. Asynapsis marker HORMAD1 is diffusely distributed throughout the chromatin, and SYCP1, which normally marks synapsed axes, is largely absent. Centromeric and telomeric sister chromatid cohesion are impaired. Centromere and telomere clustering occurs in the absence of STAG3, and telomere structure is not severely affected. Other cohesin proteins are present, localize throughout the STAG3-devoid chromatin, and form complexes with cohesin SMC1β. No other deficiency in a single meiosis-specific cohesin causes a phenotype as drastic as STAG3 deficiency. STAG3 emerges as the key STAG cohesin involved in major functions of meiotic cohesin.
The cohesin complex is essential for sister chromatid cohesion in mitosis and meiosis. Mice lacking STAG3/SA3, the least understood meiosis-specific cohesin subunit, are found to exhibit the strongest phenotype of any meiotic cohesin protein deficiency analyzed so far.
- Both male and female STAG3-deficient mice are sterile.
- STAG3-deficient germ cells enter meiosis but arrest at a leptotene-like chromosome stage.
- Chromosome axis formation and synapsis of homologous chromosomes is defective in STAG3-deficient germ cells.
- Both centromeric and telomeric sister chromatid cohesion are impaired in the absence of STAG3.
- The continued presence of STAG1/SA1- and STAG2/SA2-containing cohesin complexes is unable to rescue the STAG3−/− phenotypes.