The E3 ubiquitin ligase Sina regulates the assembly and disassembly of the synaptonemal complex in Drosophila females

Abstract

During early meiotic prophase, homologous chromosomes are connected along their entire lengths by a proteinaceous tripartite structure known as the synaptonemal complex (SC). Although the components that comprise the SC are predominantly studied in this canonical ribbon-like structure, they can also polymerize into repeated structures known as polycomplexes. We find that in Drosophila oocytes, the ability of SC components to assemble into canonical tripartite SC requires the E3 ubiquitin ligase Seven in absentia (Sina). In sina mutant oocytes, SC components assemble into large rod-like polycomplexes instead of proper SC. Thus, the wild-type Sina protein inhibits the polymerization of SC components, including those of the lateral element, into polycomplexes. These polycomplexes persist into meiotic stages when canonical SC has been disassembled, indicating that Sina also plays a role in controlling SC disassembly. Polycomplexes induced by loss-of-function sina mutations associate with centromeres, sites of double-strand breaks, and cohesins. Perhaps as a consequence of these associations, centromere clustering is defective and crossing over is reduced. These results suggest that while features of the polycomplexes can be recognized as SC by other components of the meiotic nucleus, polycomplexes nonetheless fail to execute core functions of canonical SC.

Author summary

Mistakes that occur during meiotic chromosome segregation can lead to fetal death or various disorders in offspring, hence proper chromosome segregation is crucial. To ensure optimal execution of this process, crossing over must occur between homologous chromosomes. Crossovers form only in the presence of a large proteinaceous structure called the synaptonemal complex (SC), which forms between homologs during early meiosis. How SC components assemble in a controlled manner into a normal ribbon-like structure between homologs is poorly understood. In female fruit flies, mutations in seven in absentia ( sina) cause SC components to self-assemble into large structures called polycomplexes, rather than into normal SC. Sina is a member of a family of E3 ubiquitin ligases, which are present in a number of organisms and target other proteins for degradation. We propose that there are proteins that promote the assembly of SC components into polycomplexes, and that Sina is required to degrade such proteins, allowing the normal assembly of SC components between homologous chromosomes.