High impact information on NDC1

• We describe the phenotypes caused by a cold-sensitive lethal mutation (ndc1-1) that defines the NDC1 gene of yeast [1].
• Meiosis II, but not meiosis I, is sensitive to the ndc1-1 defect, suggesting that NDC1 is required for some feature common to mitosis and meiosis II. ndc1-1 appears to define a new class of cell cycle gene required for the attachment of chromosomes to the spindle pole [1].
• We show by RNA interference (RNAi) and biochemical depletion that NDC1 plays an important role in NPC and NE assembly in vivo and in vitro [2].
• The conserved transmembrane nucleoporin NDC1 is required for nuclear pore complex assembly in vertebrate cells [2].
• However, the role of Ndc1p in NPC assembly is partially redundant with Pom152p, as cells lacking both of these proteins show enhanced NPC disruption [3].

Biological context of NDC1

• Importantly, these cells exhibit a "dead" SPB phenotype, similar to cells mutant in MPS2, NDC1, or BBP1 [4].
• Mutations in NDC1 or altered NDC1 gene dosage lead to genetic instability [13,14] [5].
• Thus, both increased and decreased NDC1 dosage can lead to aneuploidy [6].
• Saccharomyces cerevisiae cells are exquisitely sensitive to altered dosage of the spindle pole body duplication gene, NDC1 [6].
• We show that the NDC1 locus is haploinsufficient because diploid yeast cells cannot survive with a single chromosomal copy of the NDC1 gene [6].

Anatomical context of NDC1

• We report a novel connection between nuclear pore complexes (NPCs) and spindle pole bodies (SPBs) revealed by our studies of the Saccharomyces cerevisiae NDC1 gene [7].
• Mutation of either the yeast MPS2 or the NDC1 gene leads to identical spindle pole body (SPB) duplication defects: The newly formed SPB is improperly inserted into the nuclear envelope (NE), preventing the cell from forming a bipolar mitotic spindle [8].
• Here, we characterized the genetic interactions between EAP1 and NDC1, a gene whose function is required for duplication of the spindle pole body (SPB) [12], the centrosome-equivalent organelle in yeast that functions as the centrosome [5].
• We show that Ndc1p is a shared component of NPCs and SPBs and propose a shared function in the assembly of these organelles into the NE [7].
• Limited proteolysis of yeast Ndc1p in cellular membranes confirms the orientation of its C-terminus [9].

Physical interactions of NDC1

• The Saccharomyces cerevisiae spindle pole body (SPB) component Nbp1p is required for SPB membrane insertion and interacts with the integral membrane proteins Ndc1p and Mps2p [4].

Other interactions of NDC1

• Finally, we have found that a deletion of POM152, which encodes an abundant but nonessential nucleoporin, suppresses the SPB duplication defect associated with a mutation in the NDC1 gene [7].
• Additionally, distinct spots of Ndc1p localization colocalize with a known SPB component, Spc42p [7].
• Indirect immunofluorescence microscopy shows that Ndc1p displays punctate, nuclear peripheral localization that colocalizes with a known NPC component, Nup49p [7].
• Order-of-function experiments reveal that the NDC1 function is required in G1 after alpha-factor arrest but before the arrest caused by cdc34 [10].
• Cells overexpressing NDC1 arrest with monopolar spindles and exhibit increase-in-ploidy phenotypes [6].

Analytical, diagnostic and therapeutic context of NDC1

• Immunoelectron microscopy shows that Ndc1p localizes to the regions of NPCs and SPBs that interact with the NE [7].
• Electron microscopy studies reveal that the absence of Ndc1p and Pom152p results in aberrant pores that have enlarged diameters and lack proteinaceous material, leading to an increased diffusion between the cytoplasm and the nucleus [3].

References