The data indicate that cohesin declines gradually during the long prophase arrest that precedes MI in female mammals. In aged oocytes, cohesin levels fall below the level required to stabilize chiasmata and to hold sister centromeres tightly together, leading to chromosome missegregation during MI. Cohesin loss may be amplified by a concomitant decline in the levels of the centromeric cohesin protector Sgo2. These findings indicate that cohesin is a key molecular link between female aging and chromosome missegregation during MI.

In diploid organisms, meiosis reduces the chromosome number by half during the formation of haploid gametes. During meiotic prophase, telomeres transiently cluster at a limited sector of the nuclear envelope (bouquet stage) near the spindle pole body (SPB). Cohesin is a multisubunit complex that contributes to chromosome segregation in meiosis I and II divisions. In yeast meiosis, deficiency for Rec8 cohesin subunit induces telomere clustering to persist, whereas telomere cluster–SPB colocalization is defective. These defects are rescued by expressing the mitotic cohesin Scc1 in rec8Δ meiosis, whereas bouquet-stage exit is independent of Cdc5 pololike kinase. An analysis of living Saccharomyces cerevisiae meiocytes revealed highly mobile telomeres from leptotene up to pachytene, with telomeres experiencing an actin- but not microtubule-dependent constraint of mobility during the bouquet stage. Our results suggest that cohesin is required for exit from actin polymerization–dependent telomere clustering and for linking the SPB to the telomere cluster in synaptic meiosis.

In many organisms, a synaptonemal complex (SC) intimately connects each pair of homologous chromosomes during much of the first meiotic prophase and is thought to play a role in regulating recombination. In the yeast Saccharomyces cerevisiae, the central element of each SC contains Zip1, a protein orthologous to mammalian SYCP1. To study the dynamics of SCs in living meiotic cells, a functional ZIP1::GFP fusion was introduced into yeast and analyzed by fluorescence video microscopy. During pachytene, SCs exhibited dramatic and continuous movement throughout the nucleus, traversing relatively large distances while twisting, folding, and unfolding. Chromosomal movements were accompanied by changes in the shape of the nucleus, and all movements were reversibly inhibited by the actin antagonist Latrunculin B. Normal movement required the NDJ1 gene, which encodes a meiosisspecific telomere protein needed for the attachment of telomeres to the nuclear periphery and for normal kinetics of recombination and meiosis. These results show that SC movements involve telomere attachment to the nuclear periphery and are actindependent and suggest these movements could facilitate completion of meiotic recombination.actin ͉ meiosis ͉ recombination ͉ synaptonemal complex ͉ yeast S porulation of diploid cells in the ascomycete Saccharomyces cerevisiae is accompanied by a typical meiotic cell cycle that culminates with the production of four haploid ascospores. Chromosomes pair, undergo recombination, and then segregate from each other in two successive divisions. Reciprocal recombination between homologous chromosomes takes place during prophase of the first meiotic division (prophase I) and is essential for proper segregation. In S. cerevisiae, prophase I can be divided into leptotene-, zygotene-, pachytene-, and diplotene-like substages defined by the state of chromosome pairing and condensation. During leptotene, chromosomes organize on proteinaceous axial elements, and double-strand breaks (DSBs) begin to appear in DNA, initiating recombination. At the same time, perinuclear telomeres begin to cluster near the spindle pole body (the yeast centrosome), pushing chromosomes into a bouquetlike configuration at the leptotene/zygotene transition. At zygotene, the axial elements pair or synapse at the sites of DSBs, and tripartite proteinaceous structures called synaptonemal complexes (SCs) begin to form between homologous chromosomes (1-3). At pachytene, the SCs have matured by a zipper-like mechanism into ribbon-like structures that are embedded at each end in the nuclear envelope and intimately connect each pair of homologues from end to end (3-5). Mature SCs are present for at least 1 h in strain SK1 and longer in other strains, so that pachytene accounts for a relatively large part of prophase I (6-8). In S. cerevisiae, DNA strand invasion and Holliday junction recombination intermediates are observed throughout zygotene and pachytene (9-12), suggesting that recombination is completed during pachytene, presumably when chromosomes...

Telomeres fail to attach to the nuclear envelope and lose structural integrity in cells lacking SMC1β.

To ensure correct meiotic chromosome segregation, sister chromatid cohesion (SCC) needs to be maintained from its establishment in prophase I oocytes before birth until continuation of meiosis into metaphase II upon oocyte maturation in the adult. Aging human oocytes suffer a steep increase in chromosome missegregation and aneuploidy, which may be caused by loss of SCC through slow deterioration of cohesin [1-3]. This hypothesis assumes cohesin expression in embryonic oocytes is sufficient to provide adequate long-term SCC. With increasing age, mouse oocytes deficient in the meiosis-specific cohesin SMC1β massively lose SCC and chiasmata [3, 4]. To test the deterioration hypothesis, we specifically and highly efficiently inactivated the mouse Smc1β gene at the primordial follicle stage shortly after birth when oocytes had just entered meiosis I dictyate arrest. In the adult, however, irrespective of oocyte age, chiasma positions and SCC are normal. Frequency and size of litters prove full fertility even in aged females. Thus, SMC1β cohesin needs only be expressed during prophase I prior to the primordial follicle stage to ensure SCC up to advanced age of mice.