Mouse Sycp1 functions in synaptonemal complex assembly, meiotic recombination., and XY body formation
Mouse Sycp1 functions in synaptonemal complex assembly, meiotic recombination., and XY body formation
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DOI：
10.1101/gad.329705
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发表时间：
2005-06-01
影响因子：
10.5
通讯作者：
Pastink, A
中科院分区：
文献类型：
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作者：
de Vries, FAT;de Boer, E;Pastink, A
在减数分裂前期，联会复合体（SC）紧密并列同源染色体（同系物）沿其长度沿着。SC由两个轴向元件（AE）组装而成，每个轴向元件沿着一个同源物，轴向元件通过许多横向细丝（TF）连接。我们破坏了小鼠基因编码TF蛋白Sycp 1分析TF在减数分裂染色体行为和重组的作用。Sycp 1（-/-），小鼠不育，但其他健康。Sycp 1（-/-）精母细胞形成正常的AE，它们同源排列，但不突触。大多数Sycp 1（-/-）精母细胞停滞在粗线期，而一小部分精母细胞达到双线期，或在例外情况下达到中期I。在细线期Sycp 1（-/-）精母细胞中，γ H2 AX（指示DNA损伤，包括双链断裂）似乎正常。在粗线体中，Sycp 1（-/-）精母细胞沿着每条染色体显示许多离散的γ H2 AX结构域，而γ H2 AX从野生型精母细胞的常染色体中消失。RAD 51/DMC 1、RPA和MSH 4灶（标记配对/重组中的早期和中间步骤）以与野生型相似的数量出现，但并不全部消失，MLH 1和MLH 3灶（标记交换中的晚期步骤）没有形成。在Sycp 1（-/-）小鼠的中期I中很少发生交叉。我们建议SYCP 1具有协调作用，并确保交叉的形成。出乎意料的是，Sycp 1（-/-）精母细胞没有形成XY体。
In meiotic prophase, synaptonemal complexes (SCs) closely appose homologous chromosomes (homologs) along their length. SCs are assembled from two axial elements (AEs), one along each homolog, which are connected by numerous transverse filaments (TFs). We disrupted the mouse gene encoding TF protein Sycp1 to analyze the role of TFs in meiotic chromosome behavior and recombination. Sycp1(-/-), mice are infertile, but otherwise healthy. Sycp1(-/-) spermatocytes form normal AEs, which align homologously, but do not synapse. Most Sycp1(-/-) spermatocytes arrest in pachynema, whereas a small proportion reaches diplonema, or, exceptionally, metaphase I. In leptotene Sycp1(-/-) spermatocytes, gamma H2AX (indicative of DNA damage, including double-strand breaks) appears normal. In pachynema, Sycp1(-/-) spermatocytes display a number of discrete gamma H2AX domains along each chromosome, whereas gamma H2AX disappears from autosomes in wild-type spermatocytes. RAD51/DMC1, RPA, and MSH4 foci (which mark early and intermediate steps in pairing/recombination) appear in similar numbers as in wild type, but do not all disappear, and MLH1 and MLH3 foci (which mark late steps in crossing over) are not formed. Crossovers were rare in metaphase I of Sycp1(-/-) mice. We propose that SYCP1 has a coordinating role, and ensures formation of crossovers. Unexpectedly, Sycp1(-/-) spermatocytes did not form XY bodies.