A fission yeast homolog of CDC20/p55CDC/Fizzy is required for recovery from DNA damage and genetically interacts with p34cdc2.
Successful recovery from DNA damage requires coordination of several biological processes. Eukaryotic cell cycle progression is delayed when the cells encounter DNA-damaging agents. This cell cycle delay allows the cells to cope with DNA damage by utilizing DNA repair enzymes. Thus, at least two processes, induction of the cell cycle delay and repair of damaged DNA, are coordinately required for recovery. In this study, a fission yeast rad mutant (slp1-362) was genetically investigated. In response to radiation, slp1 stops cell division; however, it does not restart it. This defect is suppressed when slp1-362 is combined with wee1-50 or cdc2-3w; in these mutants, the onset of mitosis is advanced due to the premature activation of p34cdc2. In contrast, slp1 is synthetically lethal with cdc25, nim1/cdr1, or cdr2, all of which are unable to activate the p34cdc2 kinase correctly. These genetic interactions of slp1 with cdc2 and its modulators imply that slp1 is not defective in either "induction of cell cycle delay" or "DNA repair." slp1+ may be involved in a critical process which restarts cell cycle progression after the completion of DNA repair. Molecular cloning of slp1+ revealed that slp1+ encodes a putative 488-amino-acid polypeptide exhibiting significant homology to WD-domain proteins, namely, CDC20 (budding yeast), p55CDC (human), and Fizzy (fly). A possible role of slp1+ is proposed.
Matsumoto
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Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. tmatsumo@aecom.yu.edu
D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D064199:Cdc20 Proteins; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D002455:Cell Division; D003001:Cloning, Molecular; D004249:DNA Damage / Q000502:physiology*; D004720:Endonucleases / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology; D005804:Genes, Lethal; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics* / Q000502:physiology / Q000528:radiation effects; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D015719:Single-Strand Specific DNA and RNA Endonucleases; D013172:Spores, Fungal; D013489:Suppression, Genetic; D013696:Temperature; D014466:Ultraviolet Rays
D002352:Carrier Proteins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C577504:slp1 protein, S pombe; C577488:CDC20 protein, human; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; D016203:CDC2 Protein Kinase; D004720:Endonucleases; C064162:RAD10 protein, S cerevisiae; D015719:Single-Strand Specific DNA and RNA Endonucleases