Meiotic Chromosome Pairing Is Promoted by Telomere-Led Chromosome Movements Independent of Bouquet Formation

摘要

Chromosome pairing in meiotic prophase is a prerequisite for the high fidelity of chromosome segregation that haploidizes the genome prior to gamete formation. In the budding yeast Saccharomyces cerevisiae , as in most multicellular eukaryotes, homologous pairing at the cytological level reflects the contemporaneous search for homology at the molecular level, where DNA double-strand broken ends find and interact with templates for repair on homologous chromosomes. Synapsis (synaptonemal complex formation) stabilizes pairing and supports DNA repair. The bouquet stage, where telomeres have formed a transient single cluster early in meiotic prophase, and telomere-promoted rapid meiotic prophase chromosome movements (RPMs) are prominent temporal correlates of pairing and synapsis. The bouquet has long been thought to contribute to the kinetics of pairing, but the individual roles of bouquet and RPMs are difficult to assess because of common dependencies. For example, in budding yeast RPMs and bouquet both require the broadly conserved SUN protein Mps3 as well as Ndj1 and Csm4, which link telomeres to the cytoskeleton through the intact nuclear envelope. We find that mutants in these genes provide a graded series of RPM activity: wild-type> mps3-dCC > mps3-dAR > ndj1 Δ> mps3-dNT ?=? csm4 Δ. Pairing rates are directly correlated with RPM activity even though only wild-type forms a bouquet, suggesting that RPMs promote homologous pairing directly while the bouquet plays at most a minor role in Saccharomyces cerevisiae . A new collision trap assay demonstrates that RPMs generate homologous and heterologous chromosome collisions in or before the earliest stages of prophase, suggesting that RPMs contribute to pairing by stirring the nuclear contents to aid the recombination-mediated homology search. Author Summary Sexual reproduction involves the fusion of gametes, as of a sperm and an egg, to produce the next generation. Each gamete must carry half the number of chromosomes of each parent so that the correct number is restored at fertilization. In order to orient chromosomes properly so that the two chromosomes of each pair (“homologs”) separate to opposite poles in the first meiotic division, the chromosomes first must find one another and align in close proximity (“pairing”) and then be fastened together along their lengths (“synapsis”) in meiotic prophase. Pairing is a poorly understood process that involves movement coupled with a mechanism for recognizing homology. We examine the role played by telomere-promoted chromosome movements (rapid prophase movements, or “RPMs”) and find a correlation between movement and pairing rates, suggesting that RPMs contribute directly to pairing. RPMs cause collisions between nonhomologous as well as between homologous chromosomes, suggesting that RPMs stir the nuclear contents to stimulate recombination-dependent pairing.