Medical Faculty Carl Gustav Carus, Institute of Physiological Chemistry Technische Universität Dresden, Dresden, Germany.
Medical Faculty Carl Gustav Carus, Institute of Physiological Chemistry Technische Universität Dresden, Dresden, Germany
EMBO J. 2014 Jun 2;33(11):1256-70. doi: 10.1002/embj.201387330. Epub 2014 May 5.
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.
黏合蛋白复合体对于有丝分裂和减数分裂都是必需的。个别黏合蛋白在减数分裂中具体的作用尚不完全清楚。我们报告了黏合蛋白中唯一的减数分裂特异性 STAG 成分 STAG3 的体内功能。新生成的雄性和雌性 STAG3 缺陷型小鼠均不育，减数分裂阻滞。在这些小鼠中，减数分裂染色体结构严重受损，因为没有形成真正的轴丝元件 (AE)，并且同源染色体不进行联会。轴丝蛋白 SYCP3 形成点状结构，许多与着丝粒部分重叠。联会标记物 HORMAD1 弥散分布在整个染色质中，而通常标记联会轴的 SYCP1 则大量缺失。着丝粒和端粒姐妹染色单体的黏合受到损害。在没有 STAG3 的情况下，着丝粒和端粒簇集发生，并且端粒结构没有受到严重影响。其他黏合蛋白存在于 STAG3 缺失的染色质中，并与黏合蛋白 SMC1β 形成复合物。在单一的减数分裂特异性黏合蛋白中没有其他缺陷会导致像 STAG3 缺陷那样剧烈的表型。STAG3 成为涉及减数分裂黏合蛋白主要功能的关键 STAG 黏合蛋白。
