The Spd1p S phase inhibitor can activate the DNA replication checkpoint pathway in fission yeast.
Spd1p (for S phase delayed) is a cell cycle inhibitor in Schizosaccharomyces pombe. Spd1p overexpression blocks the onset of both S phase and mitosis. In this study, we have investigated the mechanisms by which Spd1p overexpression blocks cell cycle progression, focussing on the block over mitotic onset. High levels of Spd1p lead to an increase in Y15 phosphorylation of Cdc2p and we show that the block over G(2) requires the Wee1p kinase and is dependent on the rad and chk1/cds1 checkpoint genes. We propose that high levels of Spd1p in G(2) cells activate the DNA replication checkpoint control, which leads to a Wee1p-dependent increase of Cdc2p Y15 phosphorylation blocking onset of mitosis. The Spd1p block at S phase onset may act by interfering directly with DNA replication, and also activates the G(2 )rad/hus checkpoint pathway to block mitosis.
Borgne
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Cell Cycle Laboratory, Imperial Cancer Research Found, Lincoln's Inn Fields, London, WC2A 3PX, UK. A.Borgne@icrf.icnet.uk
Nurse
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D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D004261:DNA Replication / Q000502:physiology*; D016193:G1 Phase / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D018816:Genes, cdc / Q000502:physiology*; D009687:Nuclear Proteins; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016196:S Phase / Q000502:physiology*; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins; D018631:ras Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C102445:Spd1 protein, S pombe; C106332:hus1 protein, S pombe; C090679:mik1 protein, S pombe; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; D016203:CDC2 Protein Kinase; D018631:ras Proteins