Academic journal article Genetics

Nuclear Structure and Chromosome Segregation in Drosophila Male Meiosis Depend on the Ubiquitin Ligase dTopors

Academic journal article Genetics

Nuclear Structure and Chromosome Segregation in Drosophila Male Meiosis Depend on the Ubiquitin Ligase dTopors

Article excerpt

ABSTRACT In many organisms, homolog pairing and synapsis at meiotic prophase depend on interactions between chromosomes and the nuclear membrane. Male Drosophila lack synapsis, but nonetheless, their chromosomes closely associate with the nuclear periphery at prophase I. To explore the functional significance of this association, we characterize mutations in nuclear blebber (nbl), a gene required for both spermatocyte nuclear shape and meiotic chromosome transmission. We demonstrate that nbl corresponds to dtopors, the Drosophila homolog of the mammalian dual ubiquitin/small ubiquitin-related modifier (SUMO) ligase Topors. We show that mutations in dtopors cause abnormalities in lamin localizations, centriole separation, and prophase I chromatin condensation and also cause anaphase I bridges that likely result from unresolved homolog connections. Bridge formation does not require mod(mdg4) in meiosis, suggesting that bridges do not result from misregulation of the male homolog conjunction complex. At the ultrastructural level, we observe disruption of nuclear shape, an uneven perinuclear space, and excess membranous structures. We show that dTopors localizes to the nuclear lamina at prophase, and also transiently to intranuclear foci. As a role of dtopors at gypsy insulator has been reported, we also asked whether these new alleles affected expression of the gypsy-induced mutation ct^sup 6^ and found that it was unaltered in dtopors homozygotes. Our results indicate that dTopors is required for germline nuclear structure and meiotic chromosome segregation, but in contrast, is not necessary for gypsy insulator function. We suggest that dtopors plays a structural role in spermatocyte lamina that is critical for multiple aspects of meiotic chromosome transmission.

ASSOCIATIONS between chromosomes and the nuclear envelope during meiotic prophase are a widely conserved phenomenon important for proper chromosome transmission. In many species, such interactions are required for bouquet formation, an arrangement in which telomeres cluster in association with the nuclear envelope to facilitate homolog pairing and synapsis (reviewed in Scherthan 2007). In Caenorhabditis elegans, analogous interactions between nuclear envelope proteins and chromosomes are mediated by zinc finger proteins that connect chromosomespecific pairing sites to integral nuclear membrane proteins (Phillips et al. 2009). These connections establish bridges across the nuclear envelope and allow for interactions between meiotic chromosomes and cytoskeletal actin. Chromosome movements dependent on these connections are important for homolog pairing (Sato et al. 2009).

The association of meiotic chromosomes with the nuclear periphery is particularly striking in Drosophila males, in which paired homologs occupy discreet domains closely apposed to the nuclear membrane. The relevance of this organization to meiotic chromosome segregation in this organism, however, has not been explored. Drosophila males have an unconventional meiosis in which homologs pair but do not assemble synaptonemal complex (Meyer 1960) and do not undergo crossing over. The mechanism of pairing in unknown. Pairing sites have been defined for the sex chromosomes (Mckee and Karpen 1990); however, they have not been demonstrated to associate with the nuclear envelope.

Toward understanding the relationship of nuclear structure to meiotic chromosome segregation in this organism, we have examined mutations in nbl. Mutant nbl males exhibit defects in spermatocyte nuclear shape and also show a high frequency of fourth chromosome loss (Wakimoto et al. 2004). This suggested that further characterization of nbl might reveal aspects of nuclear organization important for meiotic chromosome transmission. Here we show that the nbl gene corresponds to dtopors, the fly homolog of Topors, a mammalian tumor suppressor that has both ubiquitin and small ubiquitin-related modifier (SUMO) ligase activities (Rajendra et al. …

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