Interplay between synaptonemal complex, homologous recombination, and centromeres during mammalian meiosis.
Interplay between synaptonemal complex, homologous recombination, and centromeres during mammalian meiosis.
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DOI：
10.1371/journal.pgen.1002790
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发表时间：
2012-06
期刊：
影响因子：
4.5
通讯作者：
Hunter N
中科院分区：
文献类型：
--
作者：
Qiao H;Chen JK;Reynolds A;Höög C;Paddy M;Hunter N
联会复合体（synaptonemal complex，SC）使同源染色体对（同系物）紧密联会是减数分裂的一个基本特征。在许多生物体中，突触和同源重组是相互依赖的：重组促进SC形成，而SC是交换所必需的。此外，一些研究表明，SC组装的起始发生在随后将形成交叉的位点。然而，最近在芽殖酵母和果蝇的分析暗示了着丝粒在SC形成的启动中的特殊作用。此外，在芽殖酵母中，持续的SC依赖性着丝粒联合促进了未能通过交换连接的染色体的分离。在这里，我们研究了哺乳动物中SC，重组和着丝粒之间的相互作用。在小鼠精母细胞中，着丝粒不作为SC起始位点，并且总是突触的最后区域。然而，着丝粒是难治性的去突触在双丝体，并保持与短SC片段。由于SC依赖的着丝粒协会是在终变期前丢失，在同源分离的直接作用似乎不太可能。然而，后SC拆卸，我们发现证据的着丝粒间的连接，可以发挥更直接的作用，促进同源物的双向和分离。第二类持久性SC片段被证明是交叉依赖的。超分辨率结构照明显微镜（SIM）显示，这些结构最初连接单独的同源轴，并逐渐减少交叉的形式。因此，DNA交换（发生在粗线期）和轴重塑似乎是交叉形成的时间上不同的方面。对突触和交叉缺陷突变体Sycp 1 −/−的SIM分析表明，SC阻止了同源轴的不受调节的融合。我们认为SC片段保留在双丝稳定新生的二价体，并帮助协调当地的染色体重组，促进着丝粒和交叉功能。配子细胞，如精子和卵子，通过称为减数分裂的专门细胞分裂形成。减数分裂的基本和相互依赖的特征包括母本和父本染色体的配对、重组和分离。染色体配对以联会复合体（SC）的形成达到高潮，联会复合体是连接同源染色体的结构核心或轴的拉链状结构。虽然SC是已知的是重要的交叉重组，其功能的细节仍然是谜。在这项研究中，我们分析小鼠精母细胞SC，重组和着丝粒（结构，直接染色体分离）之间的相互作用进行调查。我们表明，SC防止染色体轴之间的不受调节的相互作用。这一功能似乎是特别重要的染色体末端和交叉点，DNA交换必须与染色体轴的结构交换协调。我们还表明，着丝粒仍然与SC的短片段后，一般染色体联会已发生。此外，我们检测到一种独特的类型的着丝粒间的连接，即使在着丝粒去突触后仍然存在。这样的连接可以促进未能交叉的染色体的分离。总之，我们的数据提供了新的见解SC的功能，并提高了在哺乳动物中类似于果蝇和芽殖酵母中描述的备份染色体分离系统的可能性。
The intimate synapsis of homologous chromosome pairs (homologs) by synaptonemal complexes (SCs) is an essential feature of meiosis. In many organisms, synapsis and homologous recombination are interdependent: recombination promotes SC formation and SCs are required for crossing-over. Moreover, several studies indicate that initiation of SC assembly occurs at sites where crossovers will subsequently form. However, recent analyses in budding yeast and fruit fly imply a special role for centromeres in the initiation of SC formation. In addition, in budding yeast, persistent SC–dependent centromere-association facilitates the disjunction of chromosomes that have failed to become connected by crossovers. Here, we examine the interplay between SCs, recombination, and centromeres in a mammal. In mouse spermatocytes, centromeres do not serve as SC initiation sites and are invariably the last regions to synapse. However, centromeres are refractory to de-synapsis during diplonema and remain associated by short SC fragments. Since SC–dependent centromere association is lost before diakinesis, a direct role in homolog segregation seems unlikely. However, post–SC disassembly, we find evidence of inter-centromeric connections that could play a more direct role in promoting homolog biorientation and disjunction. A second class of persistent SC fragments is shown to be crossover-dependent. Super-resolution structured-illumination microscopy (SIM) reveals that these structures initially connect separate homolog axes and progressively diminish as chiasmata form. Thus, DNA crossing-over (which occurs during pachynema) and axis remodeling appear to be temporally distinct aspects of chiasma formation. SIM analysis of the synapsis and crossover-defective mutant Sycp1−/− implies that SCs prevent unregulated fusion of homolog axes. We propose that SC fragments retained during diplonema stabilize nascent bivalents and help orchestrate local chromosome reorganization that promotes centromere and chiasma function. Gamete cells, such as sperm and eggs, form via the specialized cell division called meiosis. Essential and interdependent features of meiosis include the pairing, recombination, and segregation of maternal and paternal chromosomes. Chromosome pairing culminates with formation of synaptonemal complexes (SCs), zipper-like structures that connect the structural cores or axes of homologous chromosomes. Although SC is known to be important for crossover recombination, details of its function remain enigmatic. In this study, we analyze mouse spermatocytes to investigate the interplay between SC, recombination, and centromeres (the structures that direct chromosome segregation). We show that SC prevents unregulated interactions between chromosome axes. This function appears to be especially important at chromosome ends and at crossover sites where DNA exchange must be coordinated with structural exchange of chromosome axes. We also show that centromeres remain associated by short fragments of SC after general chromosome desynapsis has occurred. Furthermore, we detect a distinct type of inter-centromeric connection that persists even after centromeres desynapse. Such connections may facilitate the segregation of chromosomes that have failed to crossover. Together, our data provide new insights into the functions of SC and raise the possibility of a back-up chromosome segregation system in mammals analogous to those described in fruit flies and budding yeast.
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DOI：
10.1101/sqb.2010.75.038
发表时间：
2010
期刊：
Cold Spring Harbor symposia on quantitative biology
影响因子：
--
作者：
Black BE;Jansen LE;Foltz DR;Cleveland DW
通讯作者：
Cleveland DW
影响因子：
30.8
作者：
Guillon, H;de Massy, B
通讯作者：
de Massy, B
影响因子：
9.8
作者：
Brown, PW;Judis, L;Hassold, TJ
通讯作者：
Hassold, TJ
SYCE2是突发型复合物组件，双链断裂修复和同源重组所必需的。
影响因子：
7.8
作者：
Bolcun-Filas, Ewelina;Costa, Yael;Speed, Robert;Taggart, Mary;Benavente, Ricardo;De Rooij, Dirk G;Cooke, Howard J
通讯作者：
Cooke, Howard J
影响因子：
10.5
作者：
Cheng, Chung-Hsu;Lo, Yu-Hui;Wang, Ting-Fang
通讯作者：
Wang, Ting-Fang