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Proper chromosome segregation in meiosis I relies on the formation of connections between homologous chromosomes. Crossovers between homologs provide a connection that allows them to attach correctly to the meiosis I spindle. Tension is transmitted across the crossover when the partners attach to microtubules from opposing poles of the spindle. Tension stabilizes microtubule attachments that will pull the partners towards opposite poles at anaphase1,2. Paradoxically, in many organisms, non-crossover partners segregate correctly3. The mechanism by which non-crossover partners become bi-oriented on the meiotic spindle is unknown. Both crossover and noncrossover partners pair their centromeres in early in meiosis (prophase). In budding yeast, centromere pairing, is correlated with subsequent correct segregation of the partners4,5. The mechanism by which centromere pairing, in prophase, promotes later correct attachment of the partners to the metaphase spindle is unknown. We used live cell imaging to track the bi-orientation process of non-crossover chromosomes. We find that centromere pairing allows the establishment of connections between the partners that allows their later interdependent attachment to the meiotic spindle using tensionsensing bi-orientation machinery. Because all chromosome pairs experience centromere pairing, our findings suggest that crossover chromosomes also utilize this mechanism to achieve maximal segregation fidelity.

© 2019 the Author(s)., Faithful chromosome segregation during meiosis I depends upon the formation of connections between homologous chromosomes. Crossovers between homologs connect the partners, allowing them to attach to the meiotic spindle as a unit, such that they migrate away from one another at anaphase I. Homologous partners also become connected by pairing of their centromeres in meiotic prophase. This centromere pairing can promote proper segregation at anaphase I of partners that have failed to become joined by a crossover. Centromere pairing is mediated by synaptonemal complex (SC) proteins that persist at the centromere when the SC disassembles. Here, using mouse spermatocyte and yeast model systems, we tested the role of shugoshin in promoting meiotic centromere pairing by protecting centromeric synaptonemal components from disassembly. The results show that shugoshin protects the centromeric SC in meiotic prophase and, in anaphase, promotes the proper segregation of partner chromosomes that are not linked by a crossover., The authors thank the members of the Program in Cell Cycle and Cancer Biology for their constructive comments during this project. A.M.P. is funded by Award BFU2017-89408-R from the Spanish Ministry of Economy and Competitiveness and his program is supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia, which is cofunded by the Castilla–León autonomous government and the European Regional Development Fund (Award CLC–2017–01). R.J.P. was supported by Centers of Biomedical Research Excellence Grant GM103636 and March of Dimes Grant FY14-256. D.S.D. was supported by NIH Grant R01 GM087377.

In meiosis I, homologous chromosomes segregate away from each other–the first of two rounds of chromosome segregation that allow the formation of haploid gametes. In prophase I, homologous partners become joined along their length by the synaptonemal complex (SC) and crossovers form between the homologs to generate links called chiasmata. The chiasmata allow the homologs to act as a single unit, called a bivalent, as the chromosomes attach to the microtubules that will ultimately pull them away from each other at anaphase I. Recent studies, in several organisms, have shown that when the SC disassembles at the end of prophase, residual SC proteins remain at the homologous centromeres providing an additional link between the homologs. In budding yeast, this centromere pairing is correlated with improved segregation of the paired partners in anaphase. However, the causal relationship of prophase centromere pairing and subsequent disjunction in anaphase has been difficult to demonstrate as has been the relationship between SC assembly and the assembly of the centromere pairing apparatus. Here, a series of in-frame deletion mutants of the SC component Zip1 were used to address these questions. The identification of a separation-of-function allele that disrupts centromere pairing, but not SC assembly, has made it possible to demonstrate that centromere pairing and SC assembly have mechanistically distinct features and that the centromere pairing function of Zip1 drives disjunction of the paired partners in anaphase I., Author summary The generation of gametes requires the completion of a specialized cell division called meiosis. This division is unique in that it produces cells (gametes) with half the normal number of chromosomes (such that when two gametes fuse the normal chromosome number is restored). Chromosome number is reduced in meiosis by following a single round of chromosome duplication with two rounds of segregation. In the first round, meiosis I, homologous chromosomes first pair with each other, then attach to cellular cables, called microtubules, that pull them to opposite sides of the cell. It has long been known that the homologous partners become linked to each other by genetic recombination in a way that helps them behave as a single unit when they attach to the microtubules that will ultimately pull them apart. Recently, it was shown, in budding yeast and other organisms, that homologous partners can also pair at their centromeres. Here we show that this centromere pairing also contributes to proper segregation of the partners away from each other at meiosis I, and demonstrate that one protein involved in this process is able to participate in multiple mechanisms that help homologous chromosomes to pair with each other before being segregated in meiosis I.