Full-Length Synaptonemal Complex Grows Continuously during Meiotic Prophase in Budding Yeast Karen Voelkel-Meiman1., Sarah S. Moustafa1,2., Philippe Lefranc¸ ois2, Anne M. Villeneuve3, 1 Amy J. MacQueen * 1 Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, Connecticut, United States of America, 2 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut, United States of America, 3 Department of Developmental Biology, Stanford University, Stanford, California, United States of America Abstract The synaptonemal complex (SC) links two meiotic prophase chromosomal events: homolog pairing and crossover recombination. SC formation involves the multimeric assembly of coiled-coil proteins (Zip1 in budding yeast) at the interface of aligned homologous chromosomes. However, SC assembly is indifferent to homology and thus is normally regulated such that it occurs only subsequent to homology recognition. Assembled SC structurally interfaces with and influences the level and distribution of interhomolog crossover recombination events. Despite its involvement in dynamic chromosome behaviors such as homolog pairing and recombination, the extent to which SC, once installed, acts as an irreversible tether or maintains the capacity to remodel is not clear. Experiments presented here reveal insight into the dynamics of the full-length SC in budding yeast meiotic cells. We demonstrate that Zip1 continually incorporates into previously assembled synaptonemal complex during meiotic prophase. Moreover, post-synapsis Zip1 incorporation is sufficient to rescue the sporulation defect triggered by SCs built with a mutant version of Zip1, Zip1-4LA. Post-synapsis Zip1 incorporation occurs initially with a non-uniform spatial distribution, predominantly associated with Zip3, a component of the synapsis initiation complex that is presumed to mark a subset of crossover sites. A non-uniform dynamic architecture of the SC is observed independently of (i) synapsis initiation components, (ii) the Pch2 and Pph3 proteins that have been linked to Zip1 regulation, and (iii) the presence of a homolog. Finally, the rate of SC assembly and SC central region size increase in proportion to Zip1 copy number; this and other observations suggest that Zip1 does not exit the SC structure to the same extent that it enters. Our observations suggest that, after full-length assembly, SC central region exhibits little global turnover but maintains differential assembly dynamics at sites whose distribution is patterned by a recombination landscape. Citation: Voelkel-Meiman K, Moustafa SS, Lefranc¸ois P, Villeneuve AM, MacQueen AJ (2012) Full-Length Synaptonemal Complex Grows Continuously during Meiotic Prophase in Budding Yeast. PLoS Genet 8(10): e1002993. doi:10.1371/journal.pgen.1002993 Editor: R. Scott Hawley, Stowers Institute for Medical Research, United States of America Received May 2, 2012; Accepted August 13, 2012; Published October 11, 2012 Copyright: 2012 Voelkel-Meiman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by National Institutes of Health, grant # R00 GM084293 (to AJM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: amacqueen@wesleyan.edu . These authors contributed equally to this work. Introduction The critical events that ensure a precise reduction in chromosome ploidy at the first meiotic division occur during meiotic prophase [1,2]. Chromosomes are typically unpaired as nuclei enter meiosis, but by late prophase have established connections with their homologous partners, which ultimately allow such partners to disjoin specifically from one another at the first meiotic division (and segregate to separate daughter nuclei). Thus, a key accomplishment of meiotic prophase is the formation of stable partnerships between homologous chromosomes. The process that drives homolog pairing can be divided into two major steps: initiation and reinforcement. The molecular mecha- nism that mediates initial pairing between partner chromosomes is still unclear, but must involve the capacity to recognize homology and productively link this recognition to reinforcement of a paired association between two chromosomes. For meiotic nuclei in most organisms, homolog associations are stabilized for the long term via a crossover recombination event. DNA double-strand breaks (DSBs) are deliberately induced and undergo regulated repair during meiotic prophase; the fraction of double-strand breaks that are repaired to a crossover outcome involving the homolog’s (nonsister) chromatid ensure that homologous partner chromosomes are linked, so long as sister cohesion remains intact. A physical and functional link between homology recognition and stable maintenance of chromosomal partnerships is the synaptonemal complex (SC). SC formation (synapsis) involves the multimeric assembly of coiled-coil containing proteins; the coiled- coil containing proteins that establish the SC central region interact with themselves and with chromosome axis proteins associated with each homolog in order to ultimately generate an elaborate protein lattice at the interface of lengthwise-aligned chromosomes [2,3]. SC links initial homolog pairing with pairing maintenance by virtue of the fact that SC assembly is normally regulated such that it occurs only subsequent to homology recognition between chromosomes, whereas a fully assembled PLOS Genetics | www.plosgenetics.org 1 October 2012 | Volume 8 | Issue 10 | e1002993