Synapsis-dependent and -independent mechanisms stabilize homolog pairing during meiotic prophase in C. elegans

Abstract

Analysis of Caenorhabditis elegans syp-1 mutants reveals that both synapsis-dependent and -independent mechanisms contribute to stable, productive alignment of homologous chromosomes during meiotic prophase. Early prophase nuclei undergo normal reorganization in syp-1 mutants, and chromosomes initially pair. However, the polarized nuclear organization characteristic of early prophase persists for a prolonged period, and homologs dissociate prematurely; furthermore, the synaptonemal complex (SC) is absent. The predicted structure of SYP-1, its localization at the interface between intimately paired, lengthwise-aligned pachytene homologs, and its kinetics of localization with chromosomes indicate that SYP-1 is an SC structural component. A severe reduction in crossing over together with evidence for accumulated recombination intermediates in syp-1 mutants indicate that initial pairing is not sufficient for completion of exchange and implicates the SC in promoting crossover recombination. Persistence of polarized nuclear organization in syp-1 mutants suggests that SC polymerization may provide a motive force or signal that drives redispersal of chromosomes. Whereas our analysis suggests that the SC is required to stabilize pairing along the entire lengths of chromosomes, striking differences in peak pairing levels for opposite ends of chromosomes in syp-1 mutants reveal the existence of an additional mechanism that can promote local stabilization of pairing, independent of synapsis. At the onset of meiosis, an extensive spatial reorganization of chromosomes within the nucleus culminates in an arrangement in which homologous chromosomes are lengthwise-aligned, intimately paired, and capable of undergoing crossover recombination. For nearly all sexually reproducing organisms, the accuracy of chromosome segregation during meiosis I depends on the physical exchange between DNA molecules of homologous chromosomes provided by crossover recombination events that are completed in this context. In conjunction with sister-chromatid cohesion, crossing over results in the formation of chiasmata, which serve as mechanical connections that facilitate proper orientation and subsequent segregation of homologs toward opposite poles of the meiosis I spindle (Roeder 1997;Zickler and Kleckner 1999).Specific associations between homologs are established early in meiotic prophase and are maintained prior to and during completion of crossover recombination and chiasma formation. Initial pairing events occur soon after premeiotic S phase, and are typically accompanied by an overall spatial reorganization of the nucleus that leads to a striking polarized distribution of chromosomes and other nuclear contents (for reviews, see Zickler and Kleckner 1998;Scherthan 2001). Many or all aspects of early prophase polarization are lost upon entry into the pachytene stage of meiotic prophase, as homologous chromosomes achieve full intimate alignment with one another along their entire lengths. A hallmark feature of pachytene chromosome organization ...

Evolutionary history of the mammalian synaptonemal complex

“…In recent years then, further SC components were characterized outside the HIM-3 family which all localize in the CR of the SC (Macqueen et al 2002;Colaiacovo et al 2003;Smolikov et al 2007;Smolikov et al 2009). But a distinction between TF and CE proteins as in mammals or Drosophila is virtually infeasible.…”

“…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…”

Meiotic Transverse Filament Proteins: Essential for Crossing Over

“…TF proteins, have therefore been identified independently in only a limited number of species, namely mammalian species (SYCP1) (Meuwissen et al, 1992), budding yeast (Zip1) (Sym et al, 1993), Drosophila (C(3)G) (Page and Hawley, 2001) and Caenorhabditis (Syp-1 and Syp-2) (Colaia´covo et al, 2003;MacQueen et al, 2002). Despite their lack of amino acid sequence similarity, SYCP1, Zip1 and C(3)G have a similar structure: they are long coiled coil proteins with globular domains at both ends.…”

“…1a). 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 (Colaia´covo et al, 2003;MacQueen et al, 2002).…”

“…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).…”