Regulation of Synaptonemal Complex Assembly During Meiosis in S. cerevisiae

在减数分裂开始时，染色体启动广泛的重组，最终形成对齐。 同源染色体，由联会复合体(SC)沿其长度连接，每个都能够 正在与其合作伙伴进行重组。这一过程对于精确的染色体分离至关重要。 在有性繁殖生物体的配子形成过程中。尽管观察了一个多世纪的减数分裂 不同生物中的染色体配对和突触，基本的分子机制 减数分裂的染色体事件仍是未知的。同源染色体如何相互识别？ 这种最初的认识是如何得到加强的？同源识别如何与SC组装协调，从而使突触特定地发生在成对的染色体之间？我已经开始通过筛选调控萌芽酵母中SC组装的因素来研究这些问题。我已经确定了至少三条调节突触的分子途径。Fpr3和Rrd1蛋白独立地促进同源比对有缺陷的细胞核中多聚复合体的形成。多复合体是SC组分在染色体上的局部聚集，反映了SC聚合在染色体上的失败，经常出现在配对或重组中出现早期减数分裂缺陷的突变体中。Fpr3和Rrd1蛋白都有脯氨酸异构酶 活性，增加了Zip 1组装SC的能力受到伴侣调节的可能性 细胞核中的蛋白质。另一方面，Zip3在阻止SC在染色体上组装方面起到了作用。 当多复合体的形成受到影响并且Zip3活性缺失时(如在zip3 fpr3双突变体中)，SC组分在染色体上聚合，与同源排列无关。有趣的是，在zip3fpr3核中出现的线性SC结构起源于着丝粒区域。这表明着丝粒在协调主要的减数分裂染色体事件中的作用，并在酵母着丝粒和线虫配对中心之间画出了有趣的相似之处。由于Zip3与SC结构成分Zip1在同源比对之前的着丝粒区域共定位，可能Zip3通过调节着丝粒上的SC组装而有助于加强同源识别。这些实验使用遗传学、细胞学和生物化学的方法来问：Fpr3、Rrd1和Zip3是如何调节SC组装的？SC组装、重组和同源配对之间的分子关系是什么？

At the start of meiosis, chromosomes initiate an extensive reorganization that culminates in aligned homologous chromosomes, joined along their lengths by synaptonemal complex (SC), and each capable of undergoing recombination with its partner. This process is critical for accurate chromosome segregation during gamete formation in sexually reproducing organisms. Despite over a century of observing meiotic chromosome pairing and synapsis in diverse organisms, the molecular mechanisms underlying fundamental meiotic chromosomal events are still unknown. How do homologous chromosomes identify one another? How is this initial recognition reinforced? How is homolog recognition coordinated with SC assembly, such that synapsis occurs specifically between paired chromosomes? I have begun to investigate these questions by screening for factors that regulate SC assembly in budding yeast. I have identified at least three molecular pathways that regulate synapsis. The Fpr3 and Rrdl proteins independently promote the formation of poly complex in nuclei that are defective in homolog alignment. Polycomplexes are focal accumulations of SC components that reflect a failure in SC polymerization on chromosomes, and frequently occur in mutants with early meiotic defects in pairing or recombination. The Fpr3 and Rrdl proteins each have proline isomerase activity, raising the possibility that the capacity of Zip 1 to assemble SC is under regulation by chaperone proteins in the nucleus. Zip3, on the other hand, plays a role in preventing SC assembly on chromosomes. When polycomplex formation is compromised and Zip3 activity is missing, (as in a zip3 fpr3 double mutant), SC components polymerize on chromosomes, independent of homolog alignment. Interestingly, the linear SC structures that arise in zip3 fpr3 nuclei originate from centromere regions. This suggests a role for centromeres in coordinating major meiotic chromosomal events and draws an interesting parallel between yeast centromeres and C. elegans Pairing Centers. As Zip3 colocalizes with the SC structural component, Zipl, at centromere regions prior to homolog alignment, perhaps Zip3 contributes to reinforcing homolog recognition by regulating SC assembly at centromeres. The experiments proposed use genetic, cytological and biochemical approaches to ask: How do Fpr3, Rrdl and Zip3 regulate SC assembly? What is the molecular relationship between SC assembly, recombination and homolog pairing?