Synaptonemal complex components persist at centromeres and are required for homologous centromere pairing in mouse spermatocytes.
Synaptonemal complex components persist at centromeres and are required for homologous centromere pairing in mouse spermatocytes.
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DOI：
10.1371/journal.pgen.1002701
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发表时间：
2012-06
期刊：
影响因子：
4.5
通讯作者：
Pezza RJ
中科院分区：
文献类型：
--
作者：
Bisig CG;Guiraldelli MF;Kouznetsova A;Scherthan H;Höög C;Dawson DS;Pezza RJ
最近在简单模式生物中的研究表明，着丝粒配对对于确保高保真减数分裂染色体分离是重要的。然而，这一过程及其在高等真核生物中的调控机制尚不清楚。在这里，我们提出了第一个详细的研究小鼠精子发生中的减数分裂着丝粒配对，并将其与G2/中期I过渡的关键事件。在小鼠中，我们没有观察到在几种模式生物中观察到的着丝粒持续偶联的证据。然而，我们确实发现，端粒协会在非同源对或小团体在B型精原细胞和前细线期精母细胞，这种协会被破坏的联会复合体组件SYCP 3的删除。有趣的是，我们发现，在中期前期，染色体联会不是在着丝粒开始，和着丝粒区域是最后配对的合子期粗线期过渡。在前期后期，我们首先鉴定了位于成对着丝粒上的蛋白质。我们发现，联会复合体的中央和侧部元件和横丝的组件被保留在成对的着丝粒解体后，联会复合体沿着双线染色体臂。SYCP 1基因敲除小鼠精母细胞中着丝粒配对受阻。SYCP 1和SYCP 3的定位动力学表明，它们在促进同源着丝粒配对中发挥不同的作用。SYCP 1仅保留在配对的着丝粒上，与某些着丝粒蛋白开始在着丝粒上加载的时间一致，这与减数分裂特异性着丝粒组装中的作用一致。在从着丝粒去除SYCP 1后，SYCP 3然后在配对的着丝粒处积累，在那里它可以促进同源着丝粒的双向取向。我们建议，除了作为联会复合体组件的作用，SYCP 1和SYCP 3作用于着丝粒，以促进建立和/或维持着丝粒配对，并通过这样做，提高哺乳动物减数分裂染色体的分离保真度。减数分裂是配子发生的关键发育程序，在此期间产生单倍体配子以科普受精后发生的染色体数目加倍。在第一次减数分裂期间，同源染色体配对、重组和解离。任何这些过程中的错误通常与人类不育，自然流产和严重的非整倍性出生缺陷有关。交叉，重组的细胞学表现，提供了一个物理链接，将同源的母本和父本染色体成对，促进它们的分离，并保证每个配子只接受每个染色体的一个拷贝。然而，最近在低等真核生物中的研究表明，在没有重组的情况下，着丝粒区域之间的配对促进这些非重组减数分裂同源染色体的正确分离，并显著有助于重组染色体的分离保真度。我们在这里表明，SYCP 1和SYCP 3蛋白质所需的小鼠着丝粒配对。我们的研究结果定义了一个以前不知道在哺乳动物中发生的过程的结构和可能机制，这可能有助于确保正确数量的染色体转移到下一代。
Recent studies in simple model organisms have shown that centromere pairing is important for ensuring high-fidelity meiotic chromosome segregation. However, this process and the mechanisms regulating it in higher eukaryotes are unknown. Here we present the first detailed study of meiotic centromere pairing in mouse spermatogenesis and link it with key events of the G2/metaphase I transition. In mouse we observed no evidence of the persistent coupling of centromeres that has been observed in several model organisms. We do however find that telomeres associate in non-homologous pairs or small groups in B type spermatogonia and pre-leptotene spermatocytes, and this association is disrupted by deletion of the synaptonemal complex component SYCP3. Intriguingly, we found that, in mid prophase, chromosome synapsis is not initiated at centromeres, and centromeric regions are the last to pair in the zygotene-pachytene transition. In late prophase, we first identified the proteins that reside at paired centromeres. We found that components of the central and lateral element and transverse filaments of the synaptonemal complex are retained at paired centromeres after disassembly of the synaptonemal complex along diplotene chromosome arms. The absence of SYCP1 prevents centromere pairing in knockout mouse spermatocytes. The localization dynamics of SYCP1 and SYCP3 suggest that they play different roles in promoting homologous centromere pairing. SYCP1 remains only at paired centromeres coincident with the time at which some kinetochore proteins begin loading at centromeres, consistent with a role in assembly of meiosis-specific kinetochores. After removal of SYCP1 from centromeres, SYCP3 then accumulates at paired centromeres where it may promote bi-orientation of homologous centromeres. We propose that, in addition to their roles as synaptonemal complex components, SYCP1 and SYCP3 act at the centromeres to promote the establishment and/or maintenance of centromere pairing and, by doing so, improve the segregation fidelity of mammalian meiotic chromosomes. Meiosis is the key developmental program of gametogenesis during which haploid gametes are generated to cope with the doubling chromosome number that occurs after fertilization. During the first meiotic division, homologous chromosomes pair, recombine, and dissociate. Errors in any of these processes are commonly linked to human infertility, spontaneous abortions, and severe aneuploidy-based birth defects. Chiasmata, the cytological manifestations of recombination, provide a physical link that holds the homologous maternal and paternal chromosomes in pairs, facilitating their segregation, and that guarantees each gamete receives only one copy of each chromosome. Recently, however, studies in lower eukaryotes have suggested that, in the absence of recombination, pairing between centromeric regions promotes proper segregation of these non-recombined meiotic homologous chromosomes and contributes significantly to the segregation fidelity of chromosomes that have recombined. We show here that the SYCP1 and SYCP3 proteins are required for centromere pairing in mouse. Our findings define structures and possible mechanisms of a process that was not previously known to occur in mammals, which may act to insure that the correct numbers of chromosomes are transferred to the next generation.
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影响因子：
1.6
作者：
CHURCH, K;MOENS, PB
通讯作者：
MOENS, PB
DOI：
10.1159/000131302
发表时间：
1979-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
JAGIELLO, G;FANG, JS
通讯作者：
FANG, JS
影响因子：
9.2
作者：
Hamant, O;Golubovskaya, I;Cande, WZ
通讯作者：
Cande, WZ
影响因子：
4
作者：
Kouznetsova, A;Novak, I;Höög, C
通讯作者：
Höög, C
影响因子：
1.6
作者：
BRINKLEY, BR;BRENNER, SL;VALDIVIA, MM
通讯作者：
VALDIVIA, MM