Active chromosome movement in meiotic pairing - PROJECT SUMMARY Homologous chromosome pairing during meiosis is a central process underlying Mendelian inheritance, in which homologous chromosomes move through the nuclear interior to locate and pair with their homologs, prior to synapsis via the assembly of the synaptonemal complex (SC). Failure of this pairing process can result in aneuploidy. Much of the effort to understand meiosis has focused on determining genes involved in homology recognition and recombination, but the physical process by which chromosomes come together inside the densely packed nucleus remains poorly understood. In order to pair successfully, chromosomes must carry out a huge number of homology tests while avoiding interlocks that would prevent complete pairing. Meiotic chromosome movement is facilitated by forces, generated by the cytoskeleton and motor proteins, that in turn are coupled to telomeres through the nuclear envelope (NE), leading to large-scale active telomere-led motions. But these telomere motions are randomly directed, raising the question of how exactly they facilitate pairing. In addition to random telomere movement, the meiotic nucleus can undergo an extensive re- organization, including clustering of telomeres to form a bouquet, coupling of centromeres between non- homologous chromosomes, and pre-meiotic homolog alignment, depending on the organism. Here we will investigate the cellular mechanism of meiotic pairing by testing a set of hypotheses regarding the role of telomere-led active motion and nuclear re-organization in increasing the fidelity of pairing, reducing the extent of homology searching, and avoiding or reducing interlocks between chromosomes. Our work uses live-cell imaging combined with genetic manipulation in budding yeast as a model system.
