IRDB, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
Cell Div. 2013 Aug 22;8(1):12. doi: 10.1186/1747-1028-8-12.
Sister chromatid cohesion mediated by the cohesin complex is essential for accurate chromosome segregation during mitosis and meiosis. Loading of cohesin onto chromosomes is dependent on another protein complex called kollerin, containing Nipbl/Scc2 and Mau2/Scc4. Nipbl is an evolutionarily conserved large protein whose haploinsufficiency in humans causes a developmental disorder called Cornelia de Lange syndrome. Although the function of Nipbl homologues for chromosome cohesion in meiotic cells of non-vertebrate models has been elucidated, Nipbl has not been characterized so far in mammalian spermatocytes or oocytes.
Here we describe our analyses on the expression and localization of Nipbl in nuclei of mouse spermatocytes and oocytes at different stages of meiotic prophase. In both spermatocytes and oocytes we found that Nipbl is associated with the axial/lateral element of the synaptonemal complex (AE/LE) to which cohesin also localizes. Interestingly, Nipbl in spermatocytes, but not in oocytes, dissociates from the AE/LE at mid-pachytene stage coincident with completion of DNA double-strand break repair.
Our data propose that cohesin loading activity is maintained during early stages of meiotic prophase in mammalian spermatocytes and oocytes.
姐妹染色单体黏合由黏合蛋白复合物介导,对于有丝分裂和减数分裂过程中染色体的正确分离至关重要。黏合蛋白加载到染色体上依赖于另一个称为 kollerin 的蛋白复合物,该复合物包含 Nipbl/Scc2 和 Mau2/Scc4。Nipbl 是一种进化上保守的大型蛋白,其在人类中的杂合不足会导致一种称为 Cornelia de Lange 综合征的发育障碍。尽管非脊椎动物模型减数分裂细胞中染色体黏合的 Nipbl 同源物的功能已经阐明,但迄今为止,在哺乳动物精母细胞或卵母细胞中尚未对 Nipbl 进行表征。
在这里,我们描述了我们对 Nipbl 在不同减数前期阶段的小鼠精母细胞和卵母细胞核中的表达和定位的分析。在精母细胞和卵母细胞中,我们发现 Nipbl 与联会复合体的轴向/侧向元件(AE/LE)相关,黏合蛋白也定位于该元件。有趣的是,Nipbl 在精母细胞中,但不在卵母细胞中,在中粗线期与 DNA 双链断裂修复完成时从 AE/LE 解离。
我们的数据表明,在哺乳动物精母细胞和卵母细胞的减数前期早期,黏合蛋白加载活性得以维持。