MPS3 mediates meiotic bouquet formation in Saccharomyces cerevisiae

Abstract

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...

Sme4 coiled-coil protein mediates synaptonemal complex assembly, recombinosome relocalization, and spindle pole body morphogenesis

“…Meiosis-specific relocalization of SPB proteins has been observed for budding and fission yeasts Mps3 and Sad1 proteins, respectively, that relocate from SPB to the NE during meiotic prophase and return to the SPB at metaphase I (20,21). Also, the mouse Death InducerObliterator DIDO3 isoform moves from centrosome to the SC during meiosis, although it is likely not an intrinsic structural component of either structure (22).…”

Release of yeast telomeres from the nuclear periphery is triggered by replication and maintained by suppression of Ku-mediated anchoring

“…Emerging data suggest that mechanisms involved in positioning of telomeres may be conserved from yeast to vertebrates, at least to some extent. For example, the SUN domain proteins Mps3p and SUN2 have been identified as involved in positioning telomeres in yeast and human cells, respectively (Bupp et al 2007;Conrad et al 2007;Schmitt et al 2007). Together these data raise the possibility that DNA replication may contribute to reorganization of higher eukaryotic nuclei during events such as development and cell differentiation.…”

Meiosis-specific cohesin mediates homolog recognition in mouse spermatocytes

“…5E). In this regard, it is notable that budding yeast meiotic cells depleted for Rec8 (the sole meiotic cohesin in this organism) show pairing loss and bouquet arrest, and neither the depletion of Spo11 nor the ectopic expression of Scc1 (mitotic cohesin) suppresses this arrest (Trelles-Sticken et al 2005;Conrad et al 2007). Thus, studies in budding yeast and mice suggest the existence of a conserved ''bouquet exit checkpoint'' that might monitor chromosome pairing rather than DSB-dependent recombination.…”