Plug A W, Peters A H, Keegan K S, Hoekstra M F, de Boer P, Ashley T
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
J Cell Sci. 1998 Feb;111 ( Pt 4):413-23. doi: 10.1242/jcs.111.4.413.
Homologous chromosome synapsis and meiotic recombination are facilitated by several meiosis-specific structures: the synaptonemal complex (SC), and two types of meiotic nodules: (1) early meiotic nodules (MNs), also called zygotene nodules or early recombination nodules, and (2) late recombination nodules (RNs). The former are thought to be nucleoprotein complexes involved in the check for homology preceding, or accompanying synapsis, while the latter have been shown to be involved in reciprocal recombination. We have examined by immunocytochemistry the meiotic localization of a series of proteins at sites along the asynapsed axial elements prior to homologous synapsis and at sites along the SCs following synapsis. Several of the proteins examined have been implicated in repair/recombination and include RAD51, a mammalian homolog of the Escherichia coli RecA protein; Replication Protein-A (RPA), a single-strand DNA binding protein; and MLH1, a mismatch repair protein which is a homolog of the E. coli MutL protein. In addition two proteins were examined that have been implicated in meiotic checkpoints: ATM, the protein mutated in the human disease Ataxia Telangiectasia, and ATR, another member of the same family of PIK kinases. We present evidence that these proteins are all components of meiotic nodules and document changes in protein composition of these structures during zygonema and pachynema of meiotic prophase in mouse spermatocytes. These studies support the supposition that a subset of MNs are converted into RNs. However, our data also demonstrate changes in protein composition within the context of early MNs, suggesting a differentiation of these nodules during the process of synapsis. The same changes in protein composition occurred on both the normal X axis, which has no homologous pairing partner in spermatocytes, and on the axes of aberrant chromosomes that nonhomologously synapse during synaptic adjustment. These findings suggest that DNA sequences associated with MNs still must undergo an obligatory processing, even in the absence of interactions between homologous chromosomes.
联会复合体（SC），以及两种类型的减数分裂结节：（1）早期减数分裂结节（MNs），也称为偶线期结节或早期重组结节，和（2）晚期重组结节（RNs）。前者被认为是核蛋白复合体，参与在联会之前或伴随联会的同源性检查，而后者已被证明参与相互重组。我们通过免疫细胞化学检查了一系列蛋白质在同源联会之前沿着未联会的轴向元件的位点以及联会之后沿着SCs的位点的减数分裂定位。所检查的几种蛋白质与修复/重组有关，包括RAD51，大肠杆菌RecA蛋白的哺乳动物同源物；复制蛋白A（RPA），一种单链DNA结合蛋白；以及MLH1，一种错配修复蛋白，是大肠杆菌MutL蛋白的同源物。此外，还检查了两种与减数分裂检查点有关的蛋白质：ATM，在人类疾病共济失调毛细血管扩张症中发生突变的蛋白质，以及ATR，PIK激酶同一家族的另一个成员。我们提供证据表明这些蛋白质都是减数分裂结节的组成部分，并记录了这些结构在小鼠精母细胞减数分裂前期偶线期和粗线期期间蛋白质组成的变化。这些研究支持了一部分MNs会转变为RNs的假设。然而，我们的数据也证明了早期MNs背景下蛋白质组成的变化，表明这些结节在联会过程中发生了分化。在正常的X轴上也发生了相同的蛋白质组成变化，在精母细胞中X轴没有同源配对伙伴，并且在突触调整期间非同源联会的异常染色体的轴上也发生了相同变化。这些发现表明，与MNs相关的DNA序列即使在同源染色体之间没有相互作用的情况下仍必须经历强制性加工。
