Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions.
Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions.
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DOI：
10.1371/journal.pgen.1004071
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Hoffmann E
中科院分区：
文献类型：
--
作者：
Copsey A;Tang S;Jordan PW;Blitzblau HG;Newcombe S;Chan AC;Newnham L;Li Z;Gray S;Herbert AD;Arumugam P;Hochwagen A;Hunter N;Hoffmann E
在减数分裂过程中，染色体结构维持（SMC）复合体支持减数分裂的两个基本特征：同源重组和染色体分离。虽然减数分裂功能的凝聚素和凝聚素复合物已划定，第三SMC复合物，Smc 5/6的作用，仍然是谜。在这里，我们确定特定的，必要的减数分裂功能的Smc 5/6复合体的同源重组和调节的粘附。我们发现，Smc 5/6是丰富的着丝粒和凝聚素协会网站，它调节姐妹染色单体凝聚力和及时删除凝聚素从染色体臂，分别。smc 5/6也定位于重组热点，在那里它促进了正常的形成和决议的一个子集的联合分子中间体。在这方面，Smc 5/6的功能独立于MutLγ复合物定义的主要交叉途径。此外，我们表明，Smc 5/6是所需的XPF家族核酸内切酶，Mus 81-Mms 4 Eme 1的稳定的染色体定位。我们的数据表明，Smc 5/6复合体是需要特定的重组和染色体过程在整个减数分裂，在它的情况下，试图在细胞分裂与未解决的联合分子和残留的粘连蛋白导致严重的重组诱导的减数分裂灾难。减数分裂是一种特殊的细胞分裂，通过配子细胞（如精子和卵子）从每个亲本传递到后代的染色体数量正好减半。这需要匹配的（“同源”）染色体结合，然后分离到不同的细胞中，这样每个配子就包含一套完整的染色体。在许多生物体中，这一系列事件通过一种称为同源重组的过程诱导和修复染色体断裂而得到促进。当同源染色体进行重组时，断裂和完整的模板染色体之间匹配的DNA链在称为关节分子的修复中间体中交织在一起。在这项研究中，我们表明，一个高度保守的蛋白质复合物称为染色体5/6（Smc 5/6）复杂的结构维持是重要的调节重组模板的选择，以及为决议的联合分子，这是需要染色体分离。即使关节分子在缺乏正常Smc 5/6功能的突变体中仍然没有得到解决，细胞仍然试图分离染色体，减数分裂变得灾难性。因此，Smc 5/6突变体具有双重缺陷：未解决的关节分子的积累和未能停止减数分裂以去除这些结构。
During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastrophe. Meiosis is a specialized cell division that exactly halves the number of chromosomes transmitted from each parent to their offspring via gamete cells (such as sperm and eggs). This requires that matching (‘homologous’) chromosomes associate and then separate into different cells such that each gamete contains exactly one complete set of chromosomes. In many organisms, this sequence of events is facilitated by the induction and repair of chromosome breaks via a process called homologous recombination. As homologous chromosomes engage in recombination, matching DNA strands between broken and intact template chromosomes become intertwined in repair intermediates called Joint Molecules. In this study, we show that a highly conserved protein complex called the Structural Maintenance of Chromosomes 5/6 (Smc5/6) complex is important for regulating the choice of recombination template as well as for the resolution of Joint Molecules that is required for chromosomes to separate. Even though Joint Molecules remain unresolved in mutants that lack normal Smc5/6 function, cells still attempt to separate chromosomes and meiosis becomes catastrophic. Thus, Smc5/6 mutants have a two-fold defect: accumulation of unresolved Joint Molecules and a failure to stall meiosis in order to remove these structures.
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