Mechanistically, the nucleus positioning machinery relies on two spindle positioning pathways before anaphase: the Kar9p pathway (Kar9p/Bim1p/Myo2p) and the dynein pathway (Dyn1p/Bik1p/Kip2p).
Previous work has suggested that in contrast to the canonical spindle positioning pathways, astral MTs cannot reach the cortex of large cells to provide position cues and forces at metaphase (Mitchison et al., 2012).
One spindle positioning pathway can rescue the other, but inactivation of both Kar9p and dynein pathways impairs nuclear segregation and is lethal [14].
The other spindle positioning pathway, the dynein pathway, acts at anaphase onset and involves Bik1p (homologous to CLIP170), the kinesin-related Kip2p and the dynein heavy chain Dyn1p [18], [18].
One spindle positioning pathway, called the Kar9p pathway, is active during metaphase and involves Kar9p, Bim1p (which is related to EB1) and Myo2p (type V myosin) [2], [14], [15], [16].
Essential genes and genes from the dynein-dependent spindle positioning pathway are missing in the analysis since they could not be detected by synthetic lethality, others, such as kar9, had to be excluded from the analysis due to missing data.
The large number and variety of biological roles and their positions in pathways and networks indicate that they may contribute to tumorigenesis.
We consider functional hubs to be priority drug targets, because of their key positions in pathways regulating multiple genes whose expression is affected in disease.
On the contrary, considering relative positions in pathways (see Methods), drug targets in C.Prot displayed a significantly different profile compared to targets in general.
The data is divided into 15 core tables with details on gene description, their family and sub-family, FASTA sequences - both nucleotide and protein, patterns, profiles, chromosome positions, related pathways, single nucleotide polymorphisms (SNPs), structures and links to related databases.
