The cohesin subunit RAD21L functions in meiotic synapsis and exhibits sexual dimorphism in fertility
The cohesin subunit RAD21L functions in meiotic synapsis and exhibits sexual dimorphism in fertility
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DOI：
10.1038/emboj.2011.222
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发表时间：
2011-08-03
期刊：
影响因子：
11.4
通讯作者：
Pendas, Alberto M.
中科院分区：
文献类型：
--
作者：
Herran, Yurema;Gutierrez-Caballero, Cristina;Pendas, Alberto M.
粘连蛋白复合物是一种环形蛋白质结构，在复制后捕获两个姐妹染色单体，直到后期开始，此时该环通过分离酶对其 α-kleisin 亚基（有丝分裂时的 RAD21 和减数分裂时的 REC8）进行蛋白水解切割而打开。 RAD21L 是最近发现的一种 a-kleisin，存在于鱼类和哺乳动物中，并与粘连蛋白亚基 SMC1、SMC3 和 STAG3 发生生化相互作用。 RAD21L 沿小鼠性母细胞联会复合体的轴向元件定位。然而，它作为真正的粘连蛋白的存在及其功能作用有待体内验证。在这里，我们发现缺乏 RAD21L 的雄性小鼠在减数分裂前期 I 的同源染色体的完整突触存在缺陷，这会引起合子期停滞并导致完全无精症，从而导致不育。相比之下，RAD21L 缺陷的雌性具有生育能力，但会出现年龄依赖性不育。因此，我们的结果提供了体内证据，表明 RAD21L 对于男性生育能力至关重要，对于女性自然衰老过程中维持生育能力至关重要。 EMBO 杂志 (2011) 30, 3091-3105。 doi：10.1038/emboj.2011.222； 2011 年 7 月 8 日在线发布
The cohesin complex is a ring-shaped proteinaceous structure that entraps the two sister chromatids after replication until the onset of anaphase when the ring is opened by proteolytic cleavage of its alpha-kleisin subunit (RAD21 at mitosis and REC8 at meiosis) by separase. RAD21L is a recently identified a-kleisin that is present from fish to mammals and biochemically interacts with the cohesin subunits SMC1, SMC3 and STAG3. RAD21L localizes along the axial elements of the synaptonemal complex of mouse meiocytes. However, its existence as a bona fide cohesin and its functional role awaits in vivo validation. Here, we show that male mice lacking RAD21L are defective in full synapsis of homologous chromosomes at meiotic prophase I, which provokes an arrest at zygotene and leads to total azoospermia and consequently infertility. In contrast, RAD21L-deficient females are fertile but develop an age-dependent sterility. Thus, our results provide in vivo evidence that RAD21L is essential for male fertility and in females for the maintenance of fertility during natural aging. The EMBO Journal (2011) 30, 3091-3105. doi:10.1038/emboj.2011.222; Published online 8 July 2011