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Cohesin loading factor Nipbl localizes to chromosome axes during mammalian meiotic prophase

机译:黏着素加载因子Nipbl在哺乳动物减数分裂前期定位于染色体轴

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Background 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. Findings 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. Conclusions Our data propose that cohesin loading activity is maintained during early stages of meiotic prophase in mammalian spermatocytes and oocytes.
机译:背景技术由粘着蛋白复合物介导的姐妹染色单体凝聚对于有丝分裂和减数分裂过程中准确的染色体分离至关重要。将粘着蛋白加载到染色体上取决于另一种称为kollerin的蛋白质复合物,其中含有Nipbl / Scc2和Mau2 / Scc4。 Nipbl是一种进化保守的大蛋白,其在人类中的单倍剂量不足会导致称为Cornelia de Lange综合征的发育障碍。尽管已经阐明了Nipbl同源物在非脊椎动物模型的减数分裂细胞中对染色体凝聚的功能,但到目前为止,Nipbl尚未在哺乳动物的精母细胞或卵母细胞中得到表征。发现在这里我们描述了我们对减数分裂前期不同阶段小鼠精母细胞和卵母细胞核中Nipbl表达和定位的分析。在精母细胞和卵母细胞中,我们都发现Nipb1与粘着蛋白也定位的突触复合体(AE / LE)的轴向/侧向元素相关。有趣的是,在精子中期,精子细胞中的Nipbl从AE / LE中解离,而精子细胞中的Nipbl与DNA双链断裂修复的完成同时发生。结论我们的数据表明,在哺乳动物精母细胞和卵母细胞的减数分裂前期的早期阶段,黏附蛋白的负载活性得以维持。

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