Mouse Sycp1 functions in synaptonemal complex assembly, meiotic recombination, and XY body formation

Abstract

In meiotic prophase, synaptonemal complexes (SCs) closely appose homologous chromosomes (homologs) along their length. SCs are assembled from two axial elements (AEs), one along each homolog, which are connected by numerous transverse filaments (TFs In meiosis, two rounds of chromosome segregation follow one round of replication. The first segregation, meiosis I, is reductional, as homologous chromosomes (homologs) move to opposite poles, whereas meiosis II is equational, because sister chromatids disjoin. The disjunction of homologs is prepared during the prophase of meiosis I, when homologs pair and nonsister chromatids of homologs recombine (for review, see Zickler and Kleckner 1999). The resulting crossovers and cohesion between the sister chromatids connect the homologs and ensure their proper disjunction at meiosis I. In most analyzed eukaryotes, meiotic recombination is accompanied by the close apposition of homologs by a zipper-like proteinaceous structure, the synaptonemal complex (SC). After premeiotic S-phase, the two sister chromatids of each chromosome develop a common axial structure, the axial element (AE), which consists of a linear array of protein complexes involved in sister chromatid cohesion (cohesin complexes), associated with various additional proteins (for review, see Page and Hawley 2004). Numerous transverse filaments (TFs) then connect the AEs of two homologs (synapsis) to form an SC. Within the SC, AEs are called lateral elements (LEs). Genes encoding TF proteins have been identified in mammals (Sycp1), budding yeast (ZIP1), Drosophila (c(3)G), and Caenorhabditis (Syp-1 and Syp-2). SYCP1, Zip1, and C(3)G are long coiled-coil proteins with globular domains at both ends. Within SCs, they form parallel coiled-coil homodimers, which are embedded with their C termini in the LEs, whereas the N termini of TF protein molecules from opposite LEs overlap in the narrow region between the LEs of the two homologs. Caenorhabditis Syp-1 and Syp-2 are two short coiled-coil proteins, which possibly take the place of a single longer coiled-coil protein in other species (for review, see Page and Hawley 2004).In the three species in which it has been analyzed, Drosophila, Caenorhabditis, and yeast, TF-deficient mu-

Evolutionary history of the mammalian synaptonemal complex

“…If DSB induction has occurred normally, SYCP1 initially associates with the AEs via its C-terminus in zygotene. The formation of the AEs in leptotene is independent on SYCP1 and the CE-specific proteins (De Vries et al 2005;Bolcun-Filas et al 2007;Hamer et al 2008;Bolcun-Filas et al 2009;. But even though it occurs beforehand, a defined AE is no absolute requirement for the recruitment of SYCP1 to the chromosomes.…”

Meiotic Transverse Filament Proteins: Essential for Crossing Over

“…TF-deficient mutants have now been generated and characterized in yeast, Drosophila and Caenorhabditis and, most recently, in the mouse (de Vries et al, 2005). These mutants still initiate meiotic recombination (by induction of DNA double-strand breaks) (de Vries et al, 2005;Colaia´covo et al, 2003;Jang et al, 2003;Storlazzi et al, 1996), and align homologous chromosomes (de Vries et al, 2005; reviewed by Page and Hawley, 2003).…”

“…These mutants still initiate meiotic recombination (by induction of DNA double-strand breaks) (de Vries et al, 2005;Colaia´covo et al, 2003;Jang et al, 2003;Storlazzi et al, 1996), and align homologous chromosomes (de Vries et al, 2005; reviewed by Page and Hawley, 2003). However, in all four analyzed species crossover formation is affected in TF-deficient mutants (reviewed by Page and Figure 1.…”

“…Hawley, 2004 andZickler andKleckner, 1999). In Caenorhabditis and Drosophila meiotic crossing over is completely abolished (Colaia´covo et al, 2003;MacQueen et al, 2002;Page and Hawley, 2001), and in mouse almost completely (de Vries et al, 2005). Yeast zip1 null mutants on the other hand, still display about 30% of the wildtype level of crossing over (Sym et al, 1993).…”

“…The recently described Sycp1 knockout mouse (de Vries et al, 2005) provides new opportunities for analyzing the role of TF proteins in crossover interference, because the cytology of mouse meiosis is very well developed, and various recombination-related proteins have been identified. The positions along the chromosomes of protein complexes that mark recombination intermediates can therefore be analyzed in great detail in the mouse, so that the strength of interference between such protein complexes can be assessed.…”