The diverse roles of transverse filaments of synaptonemal complexes in meiosis

Abstract

In most eukaryotes, homologous chromosomes (homologs) are closely apposed during the prophase of the first meiotic division by a ladderlike proteinaceous structure, the synaptonemal complex (SC) [Fawcett, J Biophys Biochem Cytol 2:403-406, 1956; Moses, J Biophys Biochem Cytol 2: [215][216][217][218] 1956]. SCs consist of two proteinaceous axes, which each support the two sister chromatids of one homolog, and numerous transverse filaments (TFs), which connect the two axes. Organisms that assemble SCs perform meiotic recombination in the context of these structures. Although much information has accumulated about the composition of SCs and the pathways of meiotic crossing over, several questions remain about the role of SCs in meiosis, in particular, about the role of the TFs. In this review, we focus on possible role(s) of TFs. The interest in TF functions received new impulses from the recent characterization of TF-deficient mutants in a number of species. Intriguingly, the phenotypes of these mutants are very different, and a variety of TF functions appear to be hidden behind a façade of morphological conservation. However, in all TFdeficient mutants a specific class of crossovers that display interference is affected. TFs appear to create suitable preconditions for the formation of these crossovers in most species, but are most likely not directly involved in the interference process itself. Furthermore, TFs are important for full-length homolog alignment. (Fig. 1). Assembly and composition of synaptonemal complexesCohesins, which are proteins that mediate cohesion between sister chromatids (reviewed by Nasmyth 2005), are important for AE assembly (Klein et al. 1999;Pelttari et al. 2001). During S-phase, both in the mitotic cycle and in premeiotic S-phase, cohesins are installed in such a way that they hold the newly synthesized sister chromatids together. In the mitotic cycle, all sister chromatid cohesion is lost at the metaphase-to-anaphase transition, so that sister chromatids can disjoin. In meiosis, two chromosome segregations follow a single round of DNA-replication, and this is possible because cohesion is released in two steps (reviewed by Nasmyth 2001Nasmyth , 2005.Cohesins not only provide sister chromatid cohesion, but also participate in homologous recombination, both in the mitotic cycle and in meiosis. In mitosis, they enhance sister chromatid-based recombinational repair. In meiosis, their role is modified in such a way that homologous recombination occurs preferentially between chromatids of homologs, in most species, mainly or exclusively by a TF-dependent pathway of crossing over (reviewed by

Meiotic double strand breaks repair in sexually reproducing eukaryotes: We are not all equal

“…However it has been demonstrated that it is already detectable at late zygonema among prospective CO sites containing MSH4 or RPA foci, and that it occurs at a much higher level in pachytene among MLH1 foci. The colocalization of MSH4 and MLH1 in some early pachytene foci [46] is consistent with positioning of MLH1 foci in two steps, with MLH1 foci being recruited from weakly interfering MSH4 foci [55]. However, because MLH1 and MSH4 foci are distributed differently along the SCs, the factors determining MLH1 focus positions along wild-type SCs might differ from those determining MSH4 focus positions; thus the two levels of interference observed might be temporally and mechanistically distinct.…”

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

“…Identifying proteins residing in the central region of the SC may present a daunting problem. Although TF proteins share a conserved structure consisting of one or more coiled-coil domains and flanking globular domains (15,(45)(46)(47), they are difficult to identify because of a lack of sequence homology among organisms. However, recent demonstrations of characteristic microhomologies (48,49) and insights into the domain signatures of TF proteins (15,45,46,50) make this goal attainable.…”

Regulating double-stranded DNA break repair towards crossover or non-crossover during mammalian meiosis

“…In mammals, NCO are therefore predicted to be subject to a specific constraint as revealed by the low level of interference between Msh4 foci, whereas no interference could be detected genetically between NCO in S. cerevisiae (Malkova et al 2004). The action of Msh4 both in mammals and yeast could in fact be functionally similar and linked to interference control but operating at different times, and therefore at different stages, along the DSB repair pathway in these organisms (de Boer & Heyting 2006, Fig. 3).…”

“…The number of mouse Msh4 foci goes from 142 to 47 at mid-pachytene (Kneitz et al 2000) where it co-localizes with Mlh1 (SantucciDarmanin et al 2000). Therefore, unlike S. cerevisiae, in mammals the number of Msh4 foci exceeds the number of CO. Msh4 foci are evenly distributed, show a low level of interference and their distribution is clearly different from that of Mlh1, which shows a strong level of interference (de Boer & Heyting 2006). Mutant Msh4 or Msh5 mice show a strong synapsis defect, but have high levels of Rad51 foci (tested in Mhs4j/j mice only), possibly indicating a defect in the processing of recombination intermediates and a failure to establish or maintain stable homologous interactions (de Vries et al 1999, Kneitz et al 2000.…”