联会复合体的组成、功能及遗传控制

在多数有性生殖生物中, 减数分裂第一次分裂前期同源染色体间会形成一种复杂的超级蛋白结构--联会复合体(Synaptonemal complex, SC)。该结构与同源染色体间的配对、联会、交换、分离等过程密切相关。若其出现异常, 将可导致性母细胞大量凋亡, 宏观上即表现为生物个体不育。近年来, 该结构已成为减数分裂研究领域的一个热点, 但其控制机理至今所知还十分有限。文章对联会复合体的组成、功能及其遗传控制等情况进行概述, 并对其未来的研究进行探讨和展望。     

联会复合体:减数分裂的结构基础

减数分裂是有性生殖生物产生单倍体配子的特殊分裂方式,其第一次分裂(减数分裂I)过程中同源染色体的行为是最突出的特征。在减数分裂I,同源染色体间形成的联会复合体通过促进和调控程序性DNA双链断裂的形成和修复,确保同源染色体正确的识别、配对、重组和分离,从而为减数分裂I的顺利完成提供保障。本综述对联会复合体的组成和功能研究进展进行了回顾,探讨了联会复合体的组装如何影响程序性DNA双链断裂的修复和交叉互换的形成,并总结了与人类生殖障碍相关的联会复合体成分突变,还对该领域未来研究方向进行了展望。     

对减数分裂的新理解

减数分裂历来被认为是：同源染色体联会－重组－分离。染色体配对是其中最早的事件,配对又叫联会,联会由联会复合体（ＳＣ）引起或促进。联会复合体又是减数分裂重组所必需的。重组引起细胞学上可见的交叉,能够确保同源染色体分离。这些经典观点在９０年代受到了严重挑战,对减数分裂的许多新理解正在取而代之。按照新观点,减数分裂的过程可以用下图表示。１　同源性搜索是减数分裂的第一步减数分裂最早的事件不是同源染色体的配对,其前在细线期还发生了同源性搜索。它是在全染色体组内识别染色体上同源性位点的过程。搜索不仅仅限于染…     

联会复合体——原发无精症发病中的重要角色

联会复合体(synaptonemal complex,SC)是一种减数分裂特异性超分子蛋白质结构,与减数分裂I(改罗文)中同源染色体的凝缩、配对、重组和分离密切相关。近年来,联会复合体的研究取得了一系列重要的进展,包括在其组成成分和功能上的一些新发现。在小鼠不育模型中联会复合体及其编码基因的异常可引起精子发生障碍。更重要的是,联会复合体编码基因之一SCP3单个碱基缺失导致的无精症已在人类原发不育患者中得到证实。对联会复合体基因SCP1的进一步研究也正在进行之中。      

减数分裂染色体的行为及其分子基础

减数分裂是有性生殖生物配子产生的必需过程.在细胞进入减数分裂前,其染色体复制1次,但启动分裂后,细胞进行二次分裂,从而产生染色体数目减半的配子.减数分裂Ⅰ前期同源染色体的配对、联会、重组以及减数分裂Ⅰ后期同源染色体的分离是减数分裂的基本特征,而这些减数分裂特异事件的按时、依序发生则有赖于减数分裂Ⅰ前期程序性D N A双链断裂(D S B)的产生和以同源染色体为模板进行的同源重组修复.本文将对减数分裂特别是减数分裂Ⅰ前期染色体的行为进行简要综述,并就其分子基础和机制进行分析讨论.     

二种抗有丝分裂化合物诱发小鼠联会复合体损伤的研究

以抗有丝分裂化合物秋水仙素和对苯二酚处理雄性小鼠,分析了减数分裂前期细胞联会复合体出现的各类损伤。二种化合物在减数分裂前期都诱发各种特殊倾向性的联会复合体损伤(如联会复合体断裂、联会异常等现象)。联会复合体分析,可以作为监测减数分裂过程中源染色体联会异常所引起的染色体异常分离和染色体结构损伤的手段。 Abstract:Two anti-mitotic chemicals(colchicines and hydroquinone)were assayed for their effects on synaptonemal complex(SC)damage in male mice.The tested chemicals significantly induced SC anomalies including SC breakage,asynapsis and non-homologous.It is concluded that SC analysis could be used to pre-screen aneugenes and clastogenes in mammalian germinal cells.     

猕猴精母细胞联会复合体的银染色观察

作者以银染的雄性猕猴减数分裂标本,研究联会复合体的形成和行为,特别是性泡内X、Y染色体有规律的变化。指出常染色体联会复合体的形成开始于偶线期,成熟于粗线期,开始消失于弥散期。在粗线期可见20条清晰的常染色体联会复合体,其中1条带有呈深黑色的核仁组织者。X、Y染色体同源区段的配对,开始于早粗线期。随着粗线期的发展,由侧面配对转为端部配对状。性染色体配对的解体也比常染色体联会复合体晚,在弥散期仍清晰可见。在整个前期,X、Y的着色也比常染体联会复合体深。在一些细胞中,X染色体显示一种特殊的“发夹状”结构。这是在性染色体进化过程中X染色体由于易位得到的重复片段在粗线期同源配对的一种细胞学表现。     

二种抗有丝分裂化合物诱发小鼠联会复合体损伤的研究

以抗有丝分裂化合物秋水仙素和对苯二酚处理雄性小鼠,分析了减数分裂前期细胞联会复合体出现的各类损伤。二种化合物在减数分裂前期都诱发各种特殊倾向性的联会复合体损伤(如联会复合体断裂、联会异常等现象)。联会复合体分析,可以作为监测减数分裂过程中源染色体联会异常所引起的染色体异常分离和染色体结构损伤的手段。 Abstract:Two anti-mitotic chemicals(colchicines and hydroquinone)were assayed for their effects on synaptonemal complex(SC)damage in male mice.The tested chemicals significantly induced SC anomalies including SC breakage,asynapsis and non-homologous.It is concluded that SC analysis could be used to pre-screen aneugenes and clastogenes in mammalian germinal cells.     

甜菜夜蛾细胞分裂期染色体的观察

以精巢组织为材料,采用空气干燥法制备染色体标本,对甜菜夜蛾Spodopteraexigua有丝分裂和减数分裂染色体形态行为进行了研究。结果表明：甜菜夜蛾的染色体数目为n=31;染色体为弥散着丝粒染色体,2条染色体上存在次缢痕;晚偶线期出现染色体互锁现象;从早粗线期到晚粗线期联会复合体逐渐伸长;终变期同源染色体形成环状、端部交叉、尾尾相对的结构。     

酿酒酵母减数分裂的事件和特异性基因

减数分裂是生物体重要的有性生殖方式,它提供来自母本和父本的基因信息,产生具有生物多样性的子代,使其能够适应环境的变化而不断进化。本文简述了现已阐明的酿酒酵母减数分裂的重要事件如同源染色体配对、联会、基因重组、染色体分裂和特异性基因。在同源染色体配对的过程中现已发现了2条途径,一条由Rad51独立完成,另一条有Dmc1、Hop2、Rad51和Mnd1参与,同时Rad51也可能参与。Red1、Hop1和Zip1是联会复合体的组成成分,而联会也要求其他减数分裂的特异性基因如Hop2的参与。基因重组是减数分裂中最重要的事件,它为子代提供了新的遗传信息,是生物多样性的基础之一。Spo11、Rad52组、Dmc1、Mnd1、Msh4、Msh5、Mek1、Red1和Hop1参与了基因重组。Spo11是发现和研究得最早的启动基因重组的基因之一;Rec8、Spo13和Sgo1参与了染色体分裂的过程。     

The central region of the synaptonemal complex revealed in three dimensions

The synaptonemal complex plays a key role in pairing of homologous chromosomes during meiosis. Its gross structure was already known by conventional electron microscopy, but only recently has it been possible to reveal the synaptonemal complex in three dimensions at higher resolution by electron microscope tomography. As the molecular analysis of meiosis is developing rapidly, a more thorough understanding of the principal organization of the synaptonemal complex is essential.     

Ultrastructural analysis of chromatin in meiosis I + II of rye (Secale cereale L.)

Scanning electron microscopy (SEM) proves to be an appropriate technique for imaging chromatin organization in meiosis I and II of rye (Secale cereale) down to a resolution of a few nanometers. It could be shown for the first time that organization of basic structural elements (coiled and parallel fibers, chromomeres) changes dramatically during the progression to metaphase I and II. Controlled loosening with proteinase K (after fixation with glutaraldehyde) provides an enhanced insight into chromosome architecture even of highly condensed stages of meiosis. By selective staining with platinum blue, DNA content and distribution can be visualized within compact chromosomes as well as in a complex arrangement of fibers. Chromatin interconnecting threads, which are typically observed in prophase I between homologous and non-homologous chromosomes, stain clearly for DNA. In zygotene transversion of chromatid strands to their homologous counterparts becomes evident. In pachytene segments of synapsed and non-synapsed homologs alternate. At synapsed regions pairing is so intimate that homologous chromosomes form one filament of structural entity. Chiasmata are characterized by chromatid strands which traverse from one homolog to its counterpart. Bivalents are characteristically fused at their telomeric regions. In metaphase I and II there is no structural evidence for primary and secondary constrictions.     

Dynamics of chromosome organization and pairing during meiotic prophase in fission yeast

Interactions between homologous chromosomes (pairing, recombination) are of central importance for meiosis. We studied entire chromosomes and defined chromosomal subregions in synchronous meiotic cultures of Schizosaccharomyces pombe by fluorescence in situ hybridization. Probes of different complexity were applied to spread nuclei, to delineate whole chromosomes, to visualize repeated sequences of centromeres, telomeres, and ribosomal DNA, and to study unique sequences of different chromosomal regions. In diploid nuclei, homologous chromosomes share a joint territory even before entry into meiosis. The centromeres of all chromosomes are clustered in vegetative and meiotic prophase cells, whereas the telomeres cluster near the nucleolus early in meiosis and maintain this configuration throughout meiotic prophase. Telomeres and centromeres appear to play crucial roles for chromosome organization and pairing, both in vegetative cells and during meiosis. Homologous pairing of unique sequences shows regional differences and is most frequent near centromeres and telomeres. Multiple homologous interactions are formed independently of each other. Pairing increases during meiosis, but not all chromosomal regions become closely paired in every meiosis. There is no detectable axial compaction of chromosomes in meiotic prophase. S. pombe does not form mature synaptonemal complexes, but axial element-like structures (linear elements), which were analyzed in parallel. Their appearance coincides with pairing of interstitial chromosomal regions. Axial elements may define minimal structures required for efficient pairing and recombination of meiotic chromosomes.     

Stimulation of DNA strand exchange by the human TBPIP/Hop2-Mnd1 complex

In Saccharomyces cerevisiae, the Hop2 protein forms a complex with the Mnd1 protein and is required for the alignment of homologous chromosomes during meiosis, probably through extensive homology matching between them. The Rad51 and Dmc1 proteins, the eukaryotic RecA orthologs, promote strand exchange and may function in the extensive matching of homology within paired DNA molecules. In the present study, we purified the human TBPIP/Hop2-Mnd1 complex and found that it significantly stimulates the Dmc1- and Rad51-mediated strand exchange. The human Hop2-Mnd1 complex preferentially binds to a three-stranded DNA branch, which mimics the strand-exchange intermediate. These findings are consistent with genetic data, which showed that the Hop2 and Mnd1 proteins are required for homology matching between homologous chromosomes. Therefore, the human TBPIP/Hop2-Mnd1 complex may ensure proper pairing between homologous chromosomes through its stimulation of strand exchange during meiosis.     

Sex chromosomes, synapsis, and cohesins: a complex affair

During first meiotic prophase, homologous chromosomes are held together by the synaptonemal complex, a tripartite proteinaceous structure that extends along the entire length of meiotic bivalents. While this feature is applicable for autosomes, sex chromosomes often escape from this rule. Many species present sex chromosomes that differ between them in their morphology, length, and gene content. Moreover, in some species, sex chromosomes appear in a single dose in one of the sexes. In all of these cases, the behavior of sex chromosomes during meiosis is conspicuously affected, and this includes the assembly and dynamics of the synaptonemal complex. We review in this study the structure of the synaptonemal complex in the sex chromosomes of three groups of organisms, namely: mammals, orthopterans, and hemipterans, which present different patterns of sex chromosome structure and behavior. Of special interest is the analysis of the organization of the axial/lateral elements of the synaptonemal complex in relation to other axial structures organized along meiotic chromosomes, mainly the cohesin axis. The differences found in the behavior of both axial structures reveal that while the organization of a cohesin axis along sex chromosomes is a conserved feature in most organisms and it shows very little morphological variations, the axial/lateral elements of the synaptonemal complex present a wide range of structural modifications on these chromosomes.Electronic Supplementary Material Supplementary material is available for this article at The synaptonemal complex—50 years     

Alternative ends: telomeres and meiosis

Meiosis is a specialized type of cell division that halves the diploid number of chromosomes, yielding four haploid nuclei. Dramatic changes in chromosomal organization occur within the nucleus at the beginning of meiosis which are followed by the separation of homologous chromosomes at the first meiotic division. This is the case for telomeres that display a meiotic-specific behavior with gathering in a limited sector of the nuclear periphery. This leads to a characteristic polarized chromosomal configuration, called the "bouquet" arrangement. The widespread phenomenon of bouquet formation among eukaryotes has led to the hypothesis that it is functionally linked to the process of interactions between homologous chromosomes that are a unique feature of meiosis and are essential for proper chromosome segregation. Various studies in different model organisms have questioned the role of the telomere bouquet in chromosome pairing and recombination, and very recently in meiotic spindle formation, and have provided some clues about the molecular mechanisms that carry out this specific clustering of telomeres.     

Absence of mouse REC8 cohesin promotes synapsis of sister chromatids in meiosis

REC8 is a key component of the meiotic cohesin complex. During meiosis, cohesin is required for the establishment and maintenance of sister-chromatid cohesion, for the formation of the synaptonemal complex, and for recombination between homologous chromosomes. We show that REC8 has an essential role in mammalian meiosis, in that Rec8 null mice of both sexes have germ cell failure and are sterile. In the absence of REC8, early chromosome pairing events appear normal, but synapsis occurs in a novel fashion: between sister chromatids. This implies that a major role for REC8 in mammalian meiosis is to limit synapsis to between homologous chromosomes. In all other eukaryotic species studied to date, REC8 phenotypes have been restricted to meiosis. Unexpectedly, Rec8 null mice are born in sub-Mendelian frequencies and fail to thrive. These findings illuminate hitherto unknown REC8 functions in chromosome dynamics during mammalian meiosis and possibly in somatic development.     

Interaction between Lim15/Dmc1 and the homologue of the large subunit of CAF-1: a molecular link between recombination and chromatin assembly during meiosis

In eukaryotes, meiosis leads to genetically variable gametes through recombination between homologous chromosomes of maternal and paternal origin. Chromatin organization following meiotic recombination is critical to ensure the correct segregation of homologous chromosomes into gametes. However, the mechanism of chromatin organization after meiotic recombination is unknown. In this study we report that the meiosis-specific recombinase Lim15/Dmc1 interacts with the homologue of the largest subunit of chromatin assembly factor 1 (CAF-1) in the basidiomycete Coprinopsis cinerea (Coprinus cinereus). Using C. cinerea LIM15/DMC1 (CcLIM15) as the bait in a yeast two-hybrid screen, we have isolated the C. cinerea homologue of Cac1, the largest subunit of CAF-1 in Saccharomyces cerevisiae, and named it C. cinerea Cac1-like (CcCac1L). Two-hybrid assays confirmed that CcCac1L binds CcLim15 in vivo. beta-Galactosidase assays revealed that the N-terminus of CcCac1L preferentially interacts with CcLim15. Co-immunoprecipitation experiments showed that these proteins also interact in the crude extract of meiotic cells. Furthermore, we demonstrate that, during meiosis, CcCac1L interacts with proliferating cell nuclear antigen (PCNA), a component of the DNA synthesis machinery recently reported as an interacting partner of Lim15/Dmc1. Taken together, these results suggest a novel role of the CAF-1-PCNA complex in meiotic events. We propose that the CAF-1-PCNA complex modulates chromatin assembly following meiotic recombination.