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[email protected] Introduction In Schizosaccharomyces pombe, just as in developmentally complex metazoans, cytokinesis is mediated through the assembly and constriction of a contractile, actomyosin ring. In addition to actin, myosin, and other accessory factors that provide the mechanical force necessary for ring constriction, complex signalling 12023318” networks also exist to ensure that cytokinesis occurs at the correct location within the cell and at the correct temporal position during the course of the cell cycle. Given the importance of cytokinesis in TSU 68 cellular growth and development, it is not surprising that evidence supporting the existence of a cytokinesis monitoring system has emerged in S. pombe. This system has the capacity to both delay G2/M progression and stabilize the actomyosin ring upon perturbation of the division machinery and thus aids in the faithful and reliable execution of fission yeast cytokinesis. Critical components of the monitoring system include the Septation Initiation Network, the Cdc14p family phosphatase, Clp1p, and the Ser-2 carboxy terminal domain kinase, Lsk1p. The SIN is comprised of a complex network of proteins that are required for successful ring constriction following chromosome segregation. Clp1p, on the other hand, is a Cdc14 family phosphatase that plays an important role in SIN activation. While the loss of clp1 results in only weak cytokinesis defects under normal growth conditions, clp1D cells display a lethal multi-nucleate phenotype when treated with drugs that perturb the normal function of the actomyosin ring. These defects are in part due to the inability of clp1D cells to prolong the duration of SIN signaling. Similar to clp1D cells, lsk1D mutants appear normal under typical growth conditions, but display striking cytokinesis defects upon perturbation of the cell division machinery. Furthermore as demonstrated by genetic analysis with hypo- and hyper-active SIN mutants Lsk1p promotes SIN activation. Rather surprisingly given its role in regulating cytokinesis, lsk1 encodes a member of a multi-protein complex that specifically phosphorylates the Ser-2 residues present in the twenty-nine heptad repeats found 17062696” at the extreme carboxy terminus of the largest subunit of RNA polymerase II, Rpb1p. Lsk1p displays significant sequence similarity to human Cdk9p and budding yeast Ctk1. Human Cdk9p, together with cyclin T, forms the p-TEFb complex, while Ctk1 associates with Ctk2 and Ctk3. Both complexes target Ser-2 residues of the RNA pol II CTD and promote transcript elongation. Importantly, S. pombe cells bearing rpb1 alleles that encode 12 copies of a mutant heptad sequence in which alanine has been substituted for serine at the “two”position display cytokinesis phenotypes indistinguishable from lsk1D strains. September 2011 | Volume 6 | Issue 9 | e24694 S. Pombe Ser-2 CTD Kinase Complex These data are consistent with a model in which the CTD is indeed the critical target of Lsk1p with respect to its effects on cytokinesis, and suggests that upstream kinases might act through the CTD to selectively control the transcription of certain gene subsets. In recent years several studies have provided evidence supporting such a hypothesis. For example, work in both Schizosaccharomyces pombe and Saccharomyces cerevisiae has demonstrated that the impairment of CTD phosphorylation does not necessarily result in generalized defects in transcription or transcriptional control. On the contrary, discrete sub-sets of genes

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Author: bet-bromodomain.