c(3)G encodes a Drosophila synaptonemal complex protein

Abstract

The meiotic mutant c(3)G (crossover suppressor on 3 of Gowen) abolishes both synaptonemal complex (SC) formation and meiotic recombination, whereas mutations in the mei-W68 and mei-P22 genes prevent recombination but allow normal SC to form. These data, as well as a century of cytogenetic studies, support the argument that meiotic recombination between homologous chromosomes in Drosophila females requires synapsis and SC formation. We have cloned the c(3)G gene and shown that it encodes a protein that is structurally similar to SC proteins from yeast and mammals. Immunolocalization of the C(3)G protein, as well as the analysis of a C(3)G-eGFP expression construct, reveals that C(3)G is present in a thread-like pattern along the lengths of chromosomes in meiotic prophase, consistent with a role as an SC protein present on meiotic bivalents. The availability of a marker for SC in Drosophila allowed the investigation of the extent of synapsis in exchange-defective mutants. These studies indicate that SC formation is impaired in certain meiotic mutants and that the synaptic defect correlates with the exchange defects. Moreover, the observation of interference among the residual exchanges in these mutant oocytes implies that complete SC formation is not required for crossover interference in Drosophila. Meiotic prophase is marked by interactions between homologous chromosomes that culminate in their alignment with each other along a structure called the synaptonemal complex (SC) (von Wettstein et al. 1984;Zickler and Kleckner 1999;Walker and Hawley 2000). Synapsis and SC formation between homologs is associated with, or requisite for, the formation of exchanges between homologous sequences. These exchanges are later detectable physically as chiasmata, and genetically as recombination between loci on the chromosomes. In many meiotic systems, these genetic exchanges ensure the proper segregation of homologous chromosomes during anaphase I (Hawley 1988).The SC is an almost universally conserved meiotic structure among eukaryotes (von Wettstein et al. 1984;Zickler and Kleckner 1999). After preliminary interactions align homologous chromosomes within ∼300 nm of each other, the chromosomal axes become juxtaposed at a distance of ∼100 nm, which is bridged by the SC. Electron microscopic (EM) studies show the SC as a lattice of transverse filaments (TFs) running between the homologs. The TFs connect the central element, located in the middle of the SC, with lateral elements along the axes of the chromosomes. The connections mediated by the SC are thought to provide a means for holding homologous chromosomes together during meiotic prophase (von Wettstein et al. 1984;Walker and Hawley 2000). In addition, the SC has been proposed to function in the regulation of meiotic recombination and the formation of chiasmata (von Wettstein et al. 1984).Investigations in Saccharomyces cerevisiae, Drosophila melanogaster, and Caenorhabditis elegans have revealed a complex relationship between the SC and the initiation of recombination, whi...

Synaptonemal complex extension from clustered telomeres mediates full-length chromosome pairing in Schmidtea mediterranea

“…The SC is an essential component of this process (13). Among the most important proteins of the SC are transverse filament (TF) proteins.…”

“…Although the formation of the SC at clustered centromeres and at a small number of interstitial sites is concurrent with the establishment of chromosome pairing (9,10), the absence of the SC prevents meiotic pairing both at the centromeres and along the arms of homologous chromosomes (11)(12)(13). Moreover, SC formation is required for normal levels of DSB formation (14,15) as well as for the maturation of recombination intermediates into crossovers.…”

Evolutionary history of the mammalian synaptonemal complex

“…It was shown to be the constituent of the TFs revealing a similar domain organization to the mammalian SYCP1. C(3)G is 744 aa long and has a predicted central rod domain from aa 158 to aa 646 which is flanked by globular termini (Page and Hawley 2001). Within the SC, the protein spans the distance between the LEs and the CE and exhibits the same orientation with its N-terminus in the center of the SC and the C-terminus in the LEs (Anderson et al 2005).…”

“…chiasmata, is defective in the absence of an intact CR (Page and Hawley 2001;Macqueen et al 2002;Colaiacovo et al 2003;De Vries et al 2005;Bolcun-Filas et al 2007;Smolikov et al 2007;Hamer et al 2008;Page et al 2008;Bolcun-Filas et al 2009;Smolikov et al 2009;Schramm et al 2011). The function of the mature SC during the final processing of homologous recombination thereby might be of a dual character: 1) The LNs are generally characterized by the localization of DNA mismatch repair proteins which are homologous to the bacterial MutS and…”

Superresolution expansion microscopy reveals the three-dimensional organization of theDrosophilasynaptonemal complex

“…The TF protein, C(3)G, forms a homodimer that interacts at its N-terminal end with the N terminus of another C(3)G homodimer. The C terminus of each C(3)G homodimer is positioned within the LE (13,14), although how the C terminus interacts with the LE and other chromosome axis proteins is unclear. Immuno-EM analysis of the SC protein Corona (CONA) suggests that it runs as two parallel tracks on the outer edges of the CE (15).…”