Progression of meiotic recombination requires structural maturation of the central element of the synaptonemal complex

Abstract

The synaptonemal complex is an elaborate meiosis-specific supramolecular protein assembly that promotes chromosome synapsis and meiotic recombination. We inactivated the meiosis-specific gene Tex12 and found that TEX12 is essential for progression of meiosis in both male and female germ cells. Structural analysis of the synaptonemal complex in Tex12–/– meiocytes revealed a disrupted central element structure, a dense structure residing between the synapsed homologous chromosomes. Chromosome synapsis is initiated at multiple positions along the paired homologous chromosomes in Tex12–/– meiotic cells, but fails to propagate along the chromosomes. Furthermore, although meiotic recombination is initiated in Tex12–/– meiotic cells, these early recombination events do not develop into meiotic crossovers. Hence, the mere initiation of synapsis is not sufficient to support meiotic crossing-over. Our results show that TEX12 is a component of the central element structure of the synaptonemal complex required for propagation of synapsis along the paired homologous chromosomes and maturation of early recombination events into crossovers.

Evolutionary history of the mammalian synaptonemal complex

“…However, the phylogeny of In mammals, SYCE2 and Tex12 are supposed to act in concert and to form an own complex. As they are both essential for the elongation of synapsis (Bolcun-Filas et al 2007;Hamer et al 2008), it is called the elongation complex. Just recently, Davies et al could demonstrate the constitutive character of the human SYCE2-Tex12 complex and identified aa 57 to 165 of hSYCE2 and 49 to 123 of hTex12 to be essential for their polymerization to hetero-octamers (Davies et al 2012).…”

“…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.…”

“…Small foci of CR-like structures containing SYCP1, SYCE1 and SYCE3 could be identified between the aligned AEs in electron micrographs of Syce2 -/-and Tex12 -/-spermatocytes. Because synapsis is initiated but not extended, SYCE2 and Tex12 were hypothesized to act as an elongation complex promoting expansion of the CR over the entire length of the chromosomes (Bolcun-Filas et al 2007;Hamer et al 2008;Bolcun-Filas et al 2009). The important role of SYCP1 in the CR assembly becomes obvious in the Sycp1 -/-phenotype: AEs assemble and align in these knock-out meiocytes, but none of the CE-specific proteins can be recruited to these axes and synapsis cannot be established (De Vries et al 2005;Hamer et al 2006;.…”

“…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…”

“…The crux of these mechanisms are unknown, however, theoretically it is possible that SYCP1 alone is sufficient to start synapsis in the absence of a specialized initiation complex in basal organisms because it is able to polymerize in vitro. The mammalian SYCE2 and Tex12 in contrast are not essential for initiation but for elongation of synapsis (Bolcun-Filas et al 2007;Hamer et al 2008). Correspondingly, they form the so-called elongation complex in mammals, a very stable protein complex (Davies et al 2012).…”