Haploidization of the genome in meiosis requires that chromosomes be sorted exclusively into pairs stabilized by synaptonemal complexes (SCs) and crossovers. This sorting and pairing is accompanied by active chromosome positioning in meiotic prophase in which telomeres cluster near the spindle pole to form the bouquet before dispersing around the nuclear envelope. We now describe telomere-led rapid prophase movements (RPMs) that frequently exceed 1 microm/s and persist throughout meiotic prophase. Bouquet formation and RPMs depend on NDJ1, MPS3, and a new member of this pathway, CSM4, which encodes a meiosis-specific nuclear envelope protein required specifically for telomere mobility. RPMs initiate independently of recombination but differ quantitatively in mutants that fail to complete recombination, suggesting that RPMs respond to recombination status. Together with recombination defects described for ndj1, our observations suggest that RPMs and SCs balance the disruption and stabilization of recombinational interactions, respectively, to regulate crossing over.

In meiotic prophase, telomeres associate with the nuclear envelope and accumulate adjacent to the centrosome/spindle pole to form the chromosome bouquet, a well conserved event that in Saccharomyces cerevisiae requires the meiotic telomere protein Ndj1p. Ndj1p interacts with Mps3p, a nuclear envelope SUN domain protein that is required for spindle pole body duplication and for sister chromatid cohesion. Removal of the Ndj1p-interaction domain from MPS3 creates an ndj1⌬-like separation-of-function allele, and Ndj1p and Mps3p are codependent for stable association with the telomeres. SUN domain proteins are found in the nuclear envelope across phyla and are implicated in mediating interactions between the interior of the nucleus and the cytoskeleton. Our observations indicate a general mechanism for meiotic telomere movements.meiosis ͉ SUN ͉ telomere ͉ nondisjunction H omologous chromosome pairing and recombination during meiotic prophase are required to orient chromosomes for disjunction and haploidization during the meiotic divisions. Early in meiotic prophase, telomeres attach to and move along the nuclear envelope to concentrate transiently in one sector of the nucleus, generally adjacent to the centrosome, forming the chromosome bouquet, a widely conserved arrangement (1-7). Bouquet formation may promote homologous chromosome pairing and also may help to untangle chromosomes, to regulate recombination at telomeres, to regulate crossover distribution, to coordinate or synchronize chromosomal events by propagating signals from the telomeres, and/or to facilitate synaptonemal complex formation (see refs. 1, 5, and 7-10). Despite the wide conservation of bouquet formation, the molecular mechanisms responsible for telomere attachments and movements in meiosis are poorly understood.In Saccharomyces cerevisiae, the meiotic bouquet resembles that of multicellular organisms (11)(12)(13)(14). Ndj1p is a meiosisspecific protein that accumulates at telomeres in S. cerevisiae (15,16) and is required for bouquet formation (17). Deletion of NDJ1 delays axial element formation, homolog pairing, synapsis and onset of the first meiotic division, causes an elevated frequency of nondisjunction and of ectopic recombination, and reduces spore formation and viability (15-21). Early recombination intermediates form between homologs with wild-type kinetics in ndj1⌬, suggesting that some aspect of bouquet formation is required for the normal coupling of the molecular and cytological events of pairing (22).A large-scale two-hybrid screen (23) identified an interaction between NDJ1 and MPS3/NEP98 (24, 25). Mps3p is an essential, integral membrane protein that is concentrated at the spindle pole body (SPB), the S. cerevisiae centrosome equivalent, and is present at lower levels throughout the nuclear membrane. Mps3p is required for duplication of the SPB (24, 25) and also functions in karyogamy and in sister chromatid cohesion (25,26). The present study demonstrates a critical requirement for the Ndj1p-Mps3p interaction for bouquet forma...

During meiosis, repair of programmed DNA double-strand breaks (DSBs) by recombination promotes pairing of homologous chromosomes and their connection by crossovers. Two DNA strand-exchange proteins, Rad51 and Dmc1, are required for meiotic recombination in many organisms. Studies in budding yeast imply that Rad51 acts to regulate Dmc1's strand exchange activity, while its own exchange activity is inhibited. However, in a dmc1 mutant, elimination of inhibitory factor, Hed1, activates Rad51's strand exchange activity and results in high levels of recombination without participation of Dmc1. Here we show that Rad51-mediated meiotic recombination is not subject to regulatory processes associated with high-fidelity chromosome segregation. These include homolog bias, a process that directs strand exchange between homologs rather than sister chromatids. Furthermore, activation of Rad51 does not effectively substitute for Dmc1's chromosome pairing activity, nor does it ensure formation of the obligate crossovers required for accurate homolog segregation. We further show that Dmc1's dominance in promoting strand exchange between homologs involves repression of Rad51's strand-exchange activity. This function of Dmc1 is independent of Hed1, but requires the meiotic kinase, Mek1. Hed1 makes a relatively minor contribution to homolog bias, but nonetheless this is important for normal morphogenesis of synaptonemal complexes and efficient crossing-over especially when DSB numbers are decreased. Super-resolution microscopy shows that Dmc1 also acts to organize discrete complexes of a Mek1 partner protein, Red1, into clusters along lateral elements of synaptonemal complexes; this activity may also contribute to homolog bias. Finally, we show that when interhomolog bias is defective, recombination is buffered by two feedback processes, one that increases the fraction of events that yields crossovers, and a second that we propose involves additional DSB formation in response to defective homolog interactions. Thus, robust crossover homeostasis is conferred by integrated regulation at initiation, strand-exchange and maturation steps of meiotic recombination.