Meiotic cohesin SMC1β provides prophase I centromeric cohesion and is required for multiple synapsis-associated functions.
Meiotic cohesin SMC1β provides prophase I centromeric cohesion and is required for multiple synapsis-associated functions.
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DOI：
10.1371/journal.pgen.1003985
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Jessberger R
中科院分区：
文献类型：
--
作者：
Biswas U;Wetzker C;Lange J;Christodoulou EG;Seifert M;Beyer A;Jessberger R
黏连蛋白亚基SMC 1 β是减数分裂所必需的特异性亚基。以往的研究表明SMC 1 β在决定联会复合体（SC）的轴环结构、提供中期I及以后的姐妹染色单体凝聚（SCC）、保护端粒结构和突触中的功能。然而，一些中心问题仍然没有得到解答，并涉及SMC 1 β在SCC和突触中的作用以及与这两个过程相关的过程。在这里，我们表明，SMC 1 β基本上支持前期I SCC在着丝粒，但不沿着染色体臂。非磷酸化的SMC 1 α提供了I期前期的臂内聚和部分着丝粒内聚。除了支持常染色体的突触外，SMC 1 β还需要突触和性染色体的沉默。在不存在SMC 1 β的情况下，沉默因子γ H2 AX仍然与不联会常染色体相关，并且不能定位于性染色体。微阵列表达研究显示上调的性染色体基因和许多下调的常染色体基因。在不存在SPO 11的情况下观察到的非同源染色体联合以及程序性双链断裂进一步需要SMC 1 β。这些断裂在Smc 1 β−/−精母细胞中正常产生，但它们的修复在不联会染色体上延迟。SMC 1 α单独不能支持非同源关联。结合先前的知识，已经出现了SMC 1 β的三种主要功能，这些功能对精母细胞生物学具有多种影响：SC的环轴结构的产生，同源和非同源突触，以及在早期前期I开始的SCC。哺乳动物配子通过减数分裂的产生包括两次随后的细胞分裂。第一次分裂，减数分裂I，具有高度特异性的染色体结构和行为，并需要不同的染色体相关蛋白。其中一些是减数分裂特异性的粘附蛋白，是减数分裂所必需的，但它们在减数分裂中的特殊作用还不完全清楚。我们在这里发现，SMC 1 β，一种减数分裂特异性粘附素，在减数分裂I前期已经发挥了关键作用：SMC 1 β有助于保持姐妹染色单体在着丝粒处的粘附，并支持这些细胞中存在的四个姐妹染色单体的突触。SMC 1 β是X和Y性染色体的突触所必需的。在没有SMC 1 β的情况下，常染色体不能正确突触导致基因表达的广泛改变。这导致性染色体连锁基因的表达，这些基因在这一阶段是致命的，解释了精母细胞在中前期I的死亡。结合对其他cohesin蛋白以及SMC 3和SMC 1 α的磷酸化形式的分析，本文描述了迄今为止尚未描述的减数分裂cohesin在姐妹染色单体凝聚和突触中的性质和功能。
Cohesin subunit SMC1β is specific and essential for meiosis. Previous studies showed functions of SMC1β in determining the axis-loop structure of synaptonemal complexes (SCs), in providing sister chromatid cohesion (SCC) in metaphase I and thereafter, in protecting telomere structure, and in synapsis. However, several central questions remained unanswered and concern roles of SMC1β in SCC and synapsis and processes related to these two processes. Here we show that SMC1β substantially supports prophase I SCC at centromeres but not along chromosome arms. Arm cohesion and some of centromeric cohesion in prophase I are provided by non-phosphorylated SMC1α. Besides supporting synapsis of autosomes, SMC1β is also required for synapsis and silencing of sex chromosomes. In absence of SMC1β, the silencing factor γH2AX remains associated with asynapsed autosomes and fails to localize to sex chromosomes. Microarray expression studies revealed up-regulated sex chromosome genes and many down-regulated autosomal genes. SMC1β is further required for non-homologous chromosome associations observed in absence of SPO11 and thus of programmed double-strand breaks. These breaks are properly generated in Smc1β−/− spermatocytes, but their repair is delayed on asynapsed chromosomes. SMC1α alone cannot support non-homologous associations. Together with previous knowledge, three main functions of SMC1β have emerged, which have multiple consequences for spermatocyte biology: generation of the loop-axis architecture of SCs, homologous and non-homologous synapsis, and SCC starting in early prophase I. The generation of mammalian gametes through meiosis comprises two subsequent cell divisions. The first division, meiosis I, features highly specific chromosome structures, and behavior, and requires distinct sets of chromosome-associated proteins. Cohesin proteins, of which some are meiosis-specific, are essential for meiosis, but their particular roles in meiosis are incompletely understood. We show here that SMC1β, a meiosis-specific cohesin, serves key functions already in prophase of meiosis I: SMC1β contributes to keeping sister chromatids in cohesion at their centromeres and supports synapsis of the four sister chromatids present in these cells. SMC1β is required for the synapsis of the X and Y sex chromosomes. The failure of autosomes to properly synapse in absence of SMC1β causes extensive alterations in gene expression. This leads to expression of sex chromosome-linked genes, which are lethal at this stage, explaining the death of spermatocytes in mid-prophase I. Together with the analyses of other cohesin proteins and of phosphorylated forms of SMC3 and SMC1α, this paper describes hitherto undescribed properties and functions of meiotic cohesin in sister chromatid cohesion and synapsis.
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