Department of Chromosome Biology, Max F Perutz Laboratories, University of Vienna, Vienna, Austria.
PLoS Genet. 2013;9(3):e1003335. doi: 10.1371/journal.pgen.1003335. Epub 2013 Mar 7.
Faithful chromosome segregation during meiosis I depends on the establishment of a crossover between homologous chromosomes. This requires induction of DNA double-strand breaks (DSBs), alignment of homologs, homolog association by synapsis, and repair of DSBs via homologous recombination. The success of these events requires coordination between chromosomal events and meiotic progression. The conserved SUN/KASH nuclear envelope bridge establishes transient linkages between chromosome ends and cytoskeletal forces during meiosis. In Caenorhabditis elegans, this bridge is essential for bringing homologs together and preventing nonhomologous synapsis. Chromosome movement takes place during synapsis and recombination. Concomitant with the onset of chromosome movement, SUN-1 clusters at chromosome ends associated with the nuclear envelope, and it is phosphorylated in a chk-2- and plk-2-dependent manner. Identification of all SUN-1 phosphomodifications at its nuclear N terminus allowed us to address their role in prophase I. Failures in recombination and synapsis led to persistent phosphorylations, which are required to elicit a delay in progression. Unfinished meiotic tasks elicited sustained recruitment of PLK-2 to chromosome ends in a SUN-1 phosphorylation-dependent manner that is required for continued chromosome movement and characteristic of a zygotene arrest. Furthermore, SUN-1 phosphorylation supported efficient synapsis. We propose that signals emanating from a failure to successfully finish meiotic tasks are integrated at the nuclear periphery to regulate chromosome end-led movement and meiotic progression. The single unsynapsed X chromosome in male meiosis is precluded from inducing a progression delay, and we found it was devoid of a population of phosphorylated SUN-1. This suggests that SUN-1 phosphorylation is critical to delaying meiosis in response to perturbed synapsis. SUN-1 may be an integral part of a checkpoint system to monitor establishment of the obligate crossover, inducible only in leptotene/zygotene. Unrepaired DSBs and unsynapsed chromosomes maintain this checkpoint, but a crossover intermediate is necessary to shut it down.
减数分裂 I 中染色体的正确分离取决于同源染色体之间交叉的建立。这需要诱导 DNA 双链断裂 (DSB)、同源物的对齐、通过联会使同源物相互关联,以及通过同源重组修复 DSB。这些事件的成功需要染色体事件和减数分裂进程之间的协调。保守的 SUN/KASH 核膜桥在减数分裂过程中在染色体末端和细胞骨架力之间建立瞬时连接。在秀丽隐杆线虫中,这种桥对于将同源物聚集在一起并防止非同源联会至关重要。染色体运动发生在联会和重组过程中。伴随着染色体运动的开始,SUN-1 在与核膜相关的染色体末端聚集,并以 chk-2 和 plk-2 依赖的方式磷酸化。鉴定其核 N 末端的所有 SUN-1 磷酸化修饰使我们能够解决它们在前期 I 中的作用。重组和联会的失败导致持续的磷酸化,这是引发进展延迟所必需的。未完成的减数分裂任务以 SUN-1 磷酸化依赖的方式持续招募 PLK-2 到染色体末端,这是继续染色体运动所必需的,也是合线期阻滞的特征。此外,SUN-1 磷酸化支持有效的联会。我们提出,来自未能成功完成减数分裂任务的信号在核周整合,以调节染色体末端驱动的运动和减数分裂进程。雄性减数分裂中单条未联会的 X 染色体被排除在诱导进展延迟之外,我们发现它缺乏磷酸化 SUN-1 的群体。这表明 SUN-1 磷酸化对于响应扰动的联会延迟减数分裂至关重要。SUN-1 可能是监测必需交叉建立的检查点系统的一个组成部分,仅在细线期/合线期诱导。未修复的 DSB 和未联会的染色体维持这个检查点,但交叉中间体是关闭它所必需的。