title: The Clp1p/Flp1p phosphatase ensures completion of cytokinesis in response to minor perturbation of the cell division machinery in Schizosaccharomyces pombe.
abstract: Fission yeast mutants defective in actomyosin ring formation and function exhibit a prolonged G2 delay following cytokinesis failure. This G2 delay depends on the SIN, a signaling network essential for cytokinesis, and the non-essential Cdc14p family phosphatase, Clp1p/Flp1p and has been proposed to signify a cytokinesis checkpoint mechanism. However, the physiological relevance of this proposed Clp1p/Flp1p-dependent checkpoint is unclear because all previous studies were carried out using mutations in essential actomyosin ring components under fully restrictive conditions and thus these cells would have died regardless of the presence of the checkpoint. Here we show that delays in cytokinesis caused by minor perturbations to different components of the cytokinetic machinery, which normally cause only mild defects, become lethal when Clp1p/Flp1p is inactivated. In addition, we show that Clp1p/Flp1p does not function simply to inhibit further rounds of nuclear division, but also allows damaged actomyosin rings to be maintained to facilitate completion of cell division. Ectopic activation of the SIN significantly bypasses the requirement of Clp1p/Flp1p for G2 delay as well as for completion of cytokinesis. We conclude that the Clp1p/Flp1p-dependent cytokinesis checkpoint provides a previously unrecognized cell survival advantage when the cell division apparatus is mildly perturbed.
authors.affiliation: Cell Division Laboratory, Temasek Life Sciences Laboratory, National University of Singapore, 1 Research Link, NUS, Singapore 117604, Rep. of Singapore.
authors.forename: Mithilesh
authors.initials: M
authors.lastname: Mishra
authors.forename: Jim
authors.initials: J
authors.lastname: Karagiannis
authors.forename: Susanne
authors.initials: S
authors.lastname: Trautmann
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.forename: Dannel
authors.initials: D
authors.lastname: McCollum
authors.forename: Mohan K
authors.initials: MK
authors.lastname: Balasubramanian
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology*; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D048749:Cytokinesis; D016195:G2 Phase; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008938:Mitosis; D008954:Models, Biological; D009154:Mutation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000502:physiology*; D012568:Schizosaccharomyces / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction; D013696:Temperature; D013997:Time Factors
chemical_list: D018797:Cell Cycle Proteins; D029702:Schizosaccharomyces pombe Proteins; D049452:Green Fluorescent Proteins; D000205:Actomyosin; C439269:Clp1 protein, S. pombe; D017027:Protein Tyrosine Phosphatases