Polo kinase: the choreographer of the mitotic stage?

The regulation of protein function through phosphorylation is fundamental in controlling cell cycle progression. To date, most attention has focused on the cyclin-dependent protein kinases (cdks) 1 (for review see reference 21). However, whereas the p34^(cdc)-cyclin B complex appears to regulate the mitotic "state" and in this way changes the overall organization of the cell, members of another conserved serine/threonine kinase family appears to be able to control the dynamics of cellular architecture. These are the polo-like kinases (plks) which orchestrate several mitotic events including the formation of the bipolar spindle, and at least in some organisms, the process of cytokinesis. It appears that in some of its roles the plk cooperates with p34^(cdc2) and indeed recent work (15) has suggested that one plk can help maintain the mitotic state by phosphorylating the cdc25 phosphatase that activates p34^(cdc2)

Polo kinase: the choreographer of the mitotic stage?

The regulation of protein function through phosphorylation is fundamental in controlling cell cycle progression. To date, most attention has focused on the cyclin-dependent protein kinases (cdks) 1 (for review see reference 21). However, whereas the p34^(cdc)-cyclin B complex appears to regulate the mitotic "state" and in this way changes the overall organization of the cell, members of another conserved serine/threonine kinase family appears to be able to control the dynamics of cellular architecture. These are the polo-like kinases (plks) which orchestrate several mitotic events including the formation of the bipolar spindle, and at least in some organisms, the process of cytokinesis. It appears that in some of its roles the plk cooperates with p34^(cdc2) and indeed recent work (15) has suggested that one plk can help maintain the mitotic state by phosphorylating the cdc25 phosphatase that activates p34^(cdc2)

A negative loop within the nuclear pore complex controls global chromatin organization

The nuclear pore complex (NPC) tethers chromatin to create an environment for gene regulation, but little is known about how this activity is regulated to avoid excessive tethering of the genome. Here we propose a negative regulatory loop within the NPC controlling the chromatin attachment state, in which Nup155 and Nup93 recruit Nup62 to suppress chromatin tethering by Nup155. Depletion of Nup62 severely disrupts chromatin distribution in the nuclei of female germlines and somatic cells, which can be reversed by codepleting Nup155. Thus, this universal regulatory system within the NPC is crucial to control large-scale chromatin organization in the nucleus

NHK-1 phosphorylates BAF to allow karyosome formation in the Drosophila oocyte nucleus

Accurate chromosome segregation in meiosis requires dynamic changes in chromatin organization. In Drosophila melanogaster, upon completion of recombination, meiotic chromosomes form a single, compact cluster called the karyosome in an enlarged oocyte nucleus. This clustering is also found in humans; however, the mechanisms underlying karyosome formation are not understood. In this study, we report that phosphorylation of barrier to autointegration factor (BAF) by the conserved kinase nucleosomal histone kinase-1 (NHK-1; Drosophila Vrk1) has a critical function in karyosome formation. We find that the noncatalytic domain of NHK-1 is crucial for its kinase activity toward BAF, a protein that acts as a linker between chromatin and the nuclear envelope. A reduction of NHK-1 or expression of nonphosphorylatable BAF results in ectopic association of chromosomes with the nuclear envelope in oocytes. We propose that BAF phosphorylation by NHK-1 disrupts anchorage of chromosomes to the nuclear envelope, allowing karyosome formation in oocytes. These data provide the first mechanistic insight into how the karyosome forms

The conserved kinase NHK-1 is essential for mitotic progression and unifying acentrosomal meiotic spindles in Drosophila melanogaster

Conventional centrosomes are absent from the spindle in female meiosis in many species, but it is not clear how multiple chromosomes form one shared bipolar spindle without centrosomes. We identified a female sterile mutant in which each bivalent chromosome often forms a separate bipolar metaphase I spindle. Unlike wild type, prophase I chromosomes fail to form a single compact structure within the oocyte nucleus, although the integrity of metaphase I chromosomes appears to be normal. Molecular analysis indicates that the mutant is defective in the conserved kinase nucleosomal histone kinase-1 (NHK-1). Isolation of further alleles and RNA interference in S2 cells demonstrated that NHK-1 is also required for mitotic progression. NHK-1 itself is phosphorylated in mitosis and female meiosis, suggesting that this kinase is part of the regulatory system coordinating progression of mitosis and meiosis

mini spindles: A Gene Encoding a Conserved Microtubule-Associated Protein Required for the Integrity of the Mitotic Spindle in Drosophila

We describe a new Drosophila gene, mini spindles (msps) identified in a cytological screen for mitotic mutant. Mutation in msps disrupts the structural integrity of the mitotic spindle, resulting in the formation of one or more small additional spindles in diploid cells. Nucleation of microtubules from centrosomes, metaphase alignment of chromosomes, or the focusing of spindle poles appears much less affected. The msps gene encodes a 227-kD protein with high similarity to the vertebrate microtubule-associated proteins (MAPs), human TOGp and Xenopus XMAP215, and with limited similarity to the Dis1 and STU2 proteins from fission yeast and budding yeast. Consistent with their sequence similarity, Msps protein also associates with microtubules in vitro. In the embryonic division cycles, Msps protein localizes to centrosomal regions at all mitotic stages, and spreads over the spindles during metaphase and anaphase. The absence of centrosomal staining in interphase of the cellularized embryos suggests that the interactions between Msps protein and microtubules or centrosomes may be regulated during the cell cycle