soforms. Although the S. pombe Hhp1 and Hhp2 appear to be co-evolution paralogues of yeast Hhr25p, cells lacking both genes are viable. CK1s in general and S. cerevisiae’s Hrr25 in particular have been ascribed a wide range of functions including vesicular trafficking, regulation of gene expression and DNA repair in yeast. One critical role in both yeast species is as part of a mechanism for ensuring monopolar attachment of sister kinetochores in meiosis I, a phenomenon that is essential for ensuring correct disjunction of maternal and paternal homologues. However, since E. cuniculi is not thought to undergo meiosis, this role is unlikely to be important. Budding yeast Hrr25p is also an antagonist of calcineurin signalling by regulating the nuclear localisation and hence activity of the NFAT family transcription factor Crz1p. This is a conserved Ca2+-signalling PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19796427 pathway that, amongst other processes, is involved in Tcell activation in mammals, although in S. cerevisiae it responds to a variety of environmental stresses that lead to elevated intracellular Ca2+, such as high salt and alkaline pH. Further work will be required to determine whether either of these two critical roles are the focus of the E. cuniculi CK1 homologues. CMGC family The CMGCs are the largest family of kinases in the E. cuniculi genome and 8/12 microsporidian CMGCs can be assigned homology to a number of yeast CMGCs that play essential roles. CAD26498.1 and CAD25731.1 are the microsporidian homologues of budding yeast Cdc7p, which has two paralogues in S. pombe, one of which is also essential. These kinases are DDKs, so called because they are activated by binding to a regulatory subunit, and they play a fundamental role in the activation of licensed replication origins. The other characterised microsporidian CMGCs are homologues of essential cyclin-dependent kinases such as Cdc28p/Cdc2 and Kin28p/Crk1p, the 
homologue of yeast casein kinase II, the homologue of the dual-specificity kinase Yak1p, and the homologue of yeast TTK. Of the cyclin-dependent kinases, Cdc28p/Cdc2 have clearly established fundamental roles in cell division, while the other yeast CDKs are involved in transcriptional regulation through modulating the phosphorylation state of the RNA pol II C-terminal domain. Thus although E. cuniculi does not show the full range of CDKs found in the yeasts, it 1235481-90-9 site nonetheless has homologues corresponding to both these classes, indicating that the roles of CDKs as cell cycle and RNA pol II regulators are presumably fundamental. Furthermore, at least two of the semi-orphan CMGC kinases may also belong to the Page 11 of 21 BMC Genomics 2007, 8:309 http://www.biomedcentral.com/1471-2164/8/309 Unrooted tree of the CK1 kinases of S. cerevisiae, S. pombe and E. cuniculi CDK group, although we have not classified them as such because they show considerable divergence from any of the conserved fungal CDKs. In common with many protein kinases, several CDKs require activatory phosphorylation on their Tloop threonine, which is carried out in budding yeast by Cak1p. In metazoans, this role is carried out by Cyclin H-Cdk7 rather than by a single subunit Cak1p homologue. Both systems are present in fission yeast, although the Cak1p orthologue appears to be responsible for activating the Cdk7 orthologue, which is the direct CDK activator in vivo. Since we have found an E. cuniculi orthologue of fission yeast Crk1, it is therefore likely that this Cdk7-related kinase is responsible