Synaptonemal Complex Proteins of Budding Yeast Define Reciprocal Roles in MutSγ-Mediated Crossover Formation

Abstract

During meiosis, crossover recombination creates attachments between homologous chromosomes that are essential for a precise reduction in chromosome ploidy. Many of the events that ultimately process DNA repair intermediates into crossovers during meiosis occur within the context of homologous chromosomes that are tightly aligned via a conserved structure called the synaptonemal complex (SC), but the functional relationship between SC and crossover recombination remains obscure. There exists a widespread correlation across organisms between the presence of SC proteins and successful crossing over, indicating that the SC or its building block components are procrossover factors . For example, budding yeast mutants missing the SC transverse filament component, Zip1, and mutant cells missing the Zip4 protein, which is required for the elaboration of SC, fail to form MutSg-mediated crossovers. Here we report the reciprocal phenotype-an increase in MutSg-mediated crossovers during meiosis-in budding yeast mutants devoid of the SC central element components Ecm11 or Gmc2, and in mutants expressing a version of Zip1 missing most of its N terminus. This novel phenotypic class of SC-deficient mutants demonstrates unequivocally that the tripartite SC structure is dispensable for MutSg-mediated crossover recombination in budding yeast. The excess crossovers observed in SC central element-deficient mutants are Msh4, Zip1, and Zip4 dependent, clearly indicating the existence of two classes of SC proteins-a class with procrossover function(s) that are also necessary for SC assembly and a class that is not required for crossover formation but essential for SC assembly. The latter class directly or indirectly limits MutSg-mediated crossovers along meiotic chromosomes. Our findings illustrate how reciprocal roles in crossover recombination can be simultaneously linked to the SC structure.KEYWORDS synapsis; crossover recombination; budding yeast T HE synaptonemal complex (SC) is correlated with successful interhomolog crossover formation during meiosis; mutants missing SC components nearly always exhibit a decrease in crossovers and (as a consequence) increased errors in chromosome segregation at meiosis I (Page and Hawley 2004). Transverse filaments establish a prominent component of the typically tripartite SC structure; transverse filaments are composed of coiled-coil proteins that form rod-like entities that orient perpendicular to the long axis of aligned chromosomes, bridging chromosome axes at a distance of 100 nm along the entire length of the chromosome pair (Page and Hawley 2004). The largely coiled-coil Zip1 protein is a major (and perhaps the only) transverse filament protein of the budding yeast SC (Sym et al. 1993;Dong and Roeder 2000) ( Figure 1A).Budding yeast mutants that are missing the SC transverse filament protein Zip1 lack MutSg-mediated crossovers (Novak et al. 2001;Borner et al. 2004;Voelkel-Meiman et al. 2015). Furthermore, crossover levels in double mutants missing Zip1 and any of the so-called s...

A Surveillance System Ensures Crossover Formation in C. elegans

“…Third, although it is conventionally thought that the synapsis precedes DSB/CO formation in C. elegans (because the SC can form independently of DSBs [25, 27, 42]), the actual timing of DSB/CO induction relative to synapsis is not known, but could either precede synapsis or occur contemporaneously. Lastly, a recent study in budding yeast showed that mutations in SC central element components caused increased COs suggesting an anti-CO function for the SC [45]. Our data demonstrate that there is a fundamental difference in the behavior of the SC both in spo-11 versus wild type and also on non-exchange chromosomes versus CO-positive chromosomes.…”

Understanding and Manipulating Meiotic Recombination in Plants

“…A similar increased CO rate in an SC-defective line was reported in other organisms. For example, in S. cerevisiae mutants devoid of the SC central element components Ecm11 and Gmc2, and in mutants expressing a version of Zip1 missing most of its N terminus, CO numbers also were increased (Voelkel-Meiman et al, 2016). However, it is not fully understood how the SC could influence the recombination rate.…”

Meiotic recombination modulates the structure and dynamics of the synaptonemal complex during C. elegans meiosis

“…However, organisms vary widely in the degree to which meiotic CO formation depends on SC central region proteins [20–23]. Further, the pro-CO function(s) of these proteins may be exerted locally at CO sites, not necessarily requiring assembly of extended stretches of SC [24, 25]. Conversely, SC central region proteins have also been implicated in antagonizing the formation of excess COs.…”

“…Recent work suggests that the SC central region may also play a role in limiting CO formation in S . cerevisiae , as CO numbers are similarly increased in mutants where the transverse filament protein Zip1p is present at recombination sites but cannot localize along the full length of a bivalent due to either an altered N-terminus or lack of other central region components [24]. The observation that SC central region proteins can both promote and limit COs suggests the possibility that formation of CO intermediates would lead to a change in some assayable propert(ies) of the SC.…”