Hyperosmosis enhances radiation and hydroxyurea resistance of Schizosaccharomyces pombe checkpoint mutants through the spindle checkpoint and delayed cytokinesis.
The DNA damage and stress response pathways interact to regulate cellular responses to genotoxins and environmental stresses. How these pathways interact in Schizosaccharomyces pombe is not well understood. We demonstrate that osmotic stress suppresses the DNA damage sensitivity of checkpoint mutants, and that this occurs through three distinct cell cycle delays. A delay in G2/M is dependent on Srk1. Progression through mitosis is halted by the Mad2-dependent spindle checkpoint. Finally, cytokinesis is impaired by modulating Cdc25 expression. These three delays, imposed by osmotic stress, together compensate for the loss of checkpoint signalling.
Alao
John P
JP
Department of Cell and Molecular Biology, Lundberg Laboratory, University of Gothenburg, P.O. Box 462, S-405 30 Göteborg, Sweden.
Huis In 't Veld
Pim J
PJ
Buhse
Frederike
F
Sunnerhagen
Per
P
D018797:Cell Cycle Proteins / Q000378:metabolism*; D048749:Cytokinesis / Q000187:drug effects* / Q000528:radiation effects*; D006918:Hydroxyurea / Q000633:toxicity*; D064246:Mad2 Proteins; D020928:Mitogen-Activated Protein Kinases; D009687:Nuclear Proteins; D009997:Osmotic Pressure; D012568:Schizosaccharomyces / Q000187:drug effects / Q000254:growth & development / Q000502:physiology* / Q000528:radiation effects; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D014466:Ultraviolet Rays; D020687:cdc25 Phosphatases
D018797:Cell Cycle Proteins; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C577696:mad2 protein, S pombe; C499611:SRK1 protein, S pombe; D020928:Mitogen-Activated Protein Kinases; D020687:cdc25 Phosphatases; D006918:Hydroxyurea