title: A cyclin-dependent kinase that promotes cytokinesis through modulating phosphorylation of the carboxy terminal domain of the RNA Pol II Rpb1p sub-unit.
abstract: In Schizosaccharomyces pombe, the nuclear-localized kinase, Lsk1p, promotes cytokinesis by positively regulating the Septation Initiation Network (SIN). Although a member of the cyclin-dependent kinase (CDK) family, neither a cyclin partner nor a physiological target has been identified. In this report we identify a cyclin, Lsc1p, that physically interacts and co-localizes with Lsk1p. Furthermore, lsk1Delta, lsc1Delta, as well as kinase-dead lsk1-K306R mutants, display highly similar cytokinesis defects. Lsk1p is related to CDKs that phosphorylate the carboxy-terminal domain (CTD) of the largest sub-unit of RNA polymerase II (Rpb1p). Interestingly, we find that Lsk1p and Lsc1p are required for phosphorylation of Ser-2 residues found in the heptad repeats of the CTD. To determine if Rpb1p could be a physiological target, we replaced the native rpb1 gene with a synthetic gene encoding a Rpb1p protein in which Ser-2 was substituted with the non-phosphorylatable amino-acid alanine in all heptads. Cells carrying this allele were similar to lsk1Delta mutants: They were viable, displayed genetic interactions with the SIN, and were unable to complete cytokinesis upon perturbation of the cell division machinery. We conclude that Ser-2 phosphorylation of the CTD heptads plays a novel physiological role in the regulation of cytokinesis.
authors.affiliation: cLaboratory of Cell Division, Temasek Life Sciences Laboratory, Singapore, Singapore. jkaragia@uwo.ca
authors.forename: Jim
authors.initials: J
authors.lastname: Karagiannis
authors.forename: Mohan K
authors.initials: MK
authors.lastname: Balasubramanian
mesh_terms: D000595:Amino Acid Sequence; D002453:Cell Cycle; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000201:enzymology; D017386:Sequence Homology, Amino Acid
chemical_list: D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II