title: Mik1 levels accumulate in S phase and may mediate an intrinsic link between S phase and mitosis.
abstract: Two paradigms exist for maintaining order during cell-cycle progression: intrinsic controls, where passage through one part of the cell cycle directly affects the ability to execute another, and checkpoint controls, where external pathways impose order in response to aberrant structures. By studying the mitotic inhibitor Mik1, we have identified evidence for an intrinsic link between unperturbed S phase and mitosis. We propose a model in which S/M linkage can be generated by the production and stabilization of Mik1 protein during S phase. The production of Mik1 during unperturbed S phase is independent of the Rad3- and Cds1-dependent checkpoint controls. In response to perturbed S phase, Rad3-Cds1 checkpoint controls are required to maintain high levels of Mik1, probably indirectly by extending the S phase period, where Mik1 is stable. In addition, we find that Mik1 protein can be moderately induced in response to irradiation of G(2) cells in a Chk1-dependent manner.
authors.affiliation: Medical Research Council Cell Mutation Unit, Sussex University, Falmer, Sussex, BN1 9RR, United Kingdom.
authors.forename: P U
authors.initials: PU
authors.lastname: Christensen
authors.forename: N J
authors.initials: NJ
authors.lastname: Bentley
authors.forename: R G
authors.initials: RG
authors.lastname: Martinho
authors.forename: O
authors.initials: O
authors.lastname: Nielsen
authors.forename: A M
authors.initials: AM
authors.lastname: Carr
mesh_terms: D000071877:Checkpoint Kinase 1; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000939:Epitopes / Q000378:metabolism; D005434:Flow Cytometry; D016195:G2 Phase; D006918:Hydroxyurea / Q000494:pharmacology; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D008938:Mitosis; D008954:Models, Biological; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016196:S Phase; D012568:Schizosaccharomyces / Q000201:enzymology; D029702:Schizosaccharomyces pombe Proteins; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D000939:Epitopes; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; C090679:mik1 protein, S pombe; D011505:Protein-Tyrosine Kinases; D000071877:Checkpoint Kinase 1; C000605873:Chk1 protein, S pombe; D010744:Phosphoric Monoester Hydrolases; D006918:Hydroxyurea