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. 1992 Apr;11(4):1335–1342. doi: 10.1002/j.1460-2075.1992.tb05178.x

Checkpoint controls in Schizosaccharomyces pombe: rad1.

R Rowley 1, S Subramani 1, P G Young 1
PMCID: PMC556582  PMID: 1563349

Abstract

'Checkpoint' controls ensure that the events of the cell cycle are completed in an orderly fashion. For example, such controls delay mitosis until DNA synthesis and repair of radiation-induced DNA damage are complete. The rad series of radiosensitive fission yeast mutants was examined to identify strains deficient for the DNA damage-responsive checkpoint control. Five were identified. A characterization of one (rad1-1) and the wild-type is presented. The rad1-1 mutant does not arrest after irradiation, is sensitive to killing by radiation and is not arrested by hydroxyurea, and thus is also deficient for the DNA synthesis-responsive checkpoint control. The radiosensitivity of the rad1-1 mutant was greatly reduced when irradiated and maintained for 6 h in a non-dividing (density inhibited) state, demonstrating that rad1-1 is repair proficient and radiosensitive only through failure to delay. The checkpoint controls for which rad1 is required appear to regulate G2-M progression through the activity of cdc2, here implicated in this role by the coincidence of the radiation transition point and the cdc2 execution point.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Edenberg H. J. Inhibition of DNA replication by ultraviolet light. Biophys J. 1976 Aug;16(8):849–860. doi: 10.1016/S0006-3495(76)85735-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Enoch T., Nurse P. Coupling M phase and S phase: controls maintaining the dependence of mitosis on chromosome replication. Cell. 1991 Jun 14;65(6):921–923. doi: 10.1016/0092-8674(91)90542-7. [DOI] [PubMed] [Google Scholar]
  3. Enoch T., Nurse P. Mutation of fission yeast cell cycle control genes abolishes dependence of mitosis on DNA replication. Cell. 1990 Feb 23;60(4):665–673. doi: 10.1016/0092-8674(90)90669-6. [DOI] [PubMed] [Google Scholar]
  4. Fabre F. Relation between repair mechanisms and induced mitotic recombination after UV irradiation, in the yeast Schizosaccharomyces pombe. Effects of caffeine. Mol Gen Genet. 1972;117(2):153–166. doi: 10.1007/BF00267612. [DOI] [PubMed] [Google Scholar]
  5. Fantes P. A. Dependency relations between events in mitosis in Schizosaccharomyces pombe. J Cell Sci. 1982 Jun;55:383–402. doi: 10.1242/jcs.55.1.383. [DOI] [PubMed] [Google Scholar]
  6. Fantes P. A., Nurse P. Control of the timing of cell division in fission yeast. Cell size mutants reveal a second control pathway. Exp Cell Res. 1978 Sep;115(2):317–329. doi: 10.1016/0014-4827(78)90286-0. [DOI] [PubMed] [Google Scholar]
  7. Fantes P. Epistatic gene interactions in the control of division in fission yeast. Nature. 1979 May 31;279(5712):428–430. doi: 10.1038/279428a0. [DOI] [PubMed] [Google Scholar]
  8. Fantes P., Nurse P. Control of cell size at division in fission yeast by a growth-modulated size control over nuclear division. Exp Cell Res. 1977 Jul;107(2):377–386. doi: 10.1016/0014-4827(77)90359-7. [DOI] [PubMed] [Google Scholar]
  9. Featherstone C., Russell P. Fission yeast p107wee1 mitotic inhibitor is a tyrosine/serine kinase. Nature. 1991 Feb 28;349(6312):808–811. doi: 10.1038/349808a0. [DOI] [PubMed] [Google Scholar]
  10. Feilotter H., Nurse P., Young P. G. Genetic and molecular analysis of cdr1/nim1 in Schizosaccharomyces pombe. Genetics. 1991 Feb;127(2):309–318. doi: 10.1093/genetics/127.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Friedberg E. C. Deoxyribonucleic acid repair in the yeast Saccharomyces cerevisiae. Microbiol Rev. 1988 Mar;52(1):70–102. doi: 10.1128/mr.52.1.70-102.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gentner N. E. Both caffeine-induced lethality and the negative liquid holding effect, in UV- or gamma-irradiated wild-type Schizosaccharomyces pombe, are consequences of interference with a recombinational repair process. Mol Gen Genet. 1981;181(3):283–287. doi: 10.1007/BF00425598. [DOI] [PubMed] [Google Scholar]
  13. Gould K. L., Moreno S., Tonks N. K., Nurse P. Complementation of the mitotic activator, p80cdc25, by a human protein-tyrosine phosphatase. Science. 1990 Dec 14;250(4987):1573–1576. doi: 10.1126/science.1703321. [DOI] [PubMed] [Google Scholar]
  14. Gould K. L., Nurse P. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature. 1989 Nov 2;342(6245):39–45. doi: 10.1038/342039a0. [DOI] [PubMed] [Google Scholar]
  15. Grossenbacher-Grunder A. M., Thuriaux P. Spontaneous and UV-induced recombination in radiation-sensitive mutants of Schizosaccharomyces pombe. Mutat Res. 1981 Mar;81(1):37–48. doi: 10.1016/0027-5107(81)90085-3. [DOI] [PubMed] [Google Scholar]
  16. Hannan M. A., Miller D. R., Nasim A. Changes in uv-inactivation kinetics and division delay in Schizosaccharomyces pombe strains during different growth phases. Radiat Res. 1976 Dec;68(3):469–479. [PubMed] [Google Scholar]
  17. Hartwell L. H., Weinert T. A. Checkpoints: controls that ensure the order of cell cycle events. Science. 1989 Nov 3;246(4930):629–634. doi: 10.1126/science.2683079. [DOI] [PubMed] [Google Scholar]
  18. Hindley J., Phear G. A. Sequence of the cell division gene CDC2 from Schizosaccharomyces pombe; patterns of splicing and homology to protein kinases. Gene. 1984 Nov;31(1-3):129–134. doi: 10.1016/0378-1119(84)90203-8. [DOI] [PubMed] [Google Scholar]
  19. Hittelman W. N., Rao P. N. Premature chromosome condensation. I. Visualization of x-ray-induced chromosome damage in interphase cells. Mutat Res. 1974 May;23(2):251–258. doi: 10.1016/0027-5107(74)90145-6. [DOI] [PubMed] [Google Scholar]
  20. Krakoff I. H., Brown N. C., Reichard P. Inhibition of ribonucleoside diphosphate reductase by hydroxyurea. Cancer Res. 1968 Aug;28(8):1559–1565. [PubMed] [Google Scholar]
  21. Kumagai A., Dunphy W. G. The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system. Cell. 1991 Mar 8;64(5):903–914. doi: 10.1016/0092-8674(91)90315-p. [DOI] [PubMed] [Google Scholar]
  22. Leeper D. B., Schneiderman M. H., Dewey W. C. Radiation-induced cycle delay in synchronized Chinese hamster cells: comparison between DNA synthesis and division. Radiat Res. 1973 Feb;53(2):326–337. [PubMed] [Google Scholar]
  23. Lieberman H. B., Riley R., Martel M. Isolation and initial characterization of a Schizosaccharomyces pombe mutant exhibiting temperature-dependent radiation sensitivity due to a mutation in a previously unidentified rad locus. Mol Gen Genet. 1989 Sep;218(3):554–558. doi: 10.1007/BF00332423. [DOI] [PubMed] [Google Scholar]
  24. Lundgren K., Walworth N., Booher R., Dembski M., Kirschner M., Beach D. mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2. Cell. 1991 Mar 22;64(6):1111–1122. doi: 10.1016/0092-8674(91)90266-2. [DOI] [PubMed] [Google Scholar]
  25. Lücke-Huhle C. Alpha-irradiation-induced G2 delay: a period of cell recovery. Radiat Res. 1982 Feb;89(2):298–308. [PubMed] [Google Scholar]
  26. Moreno S., Nurse P., Russell P. Regulation of mitosis by cyclic accumulation of p80cdc25 mitotic inducer in fission yeast. Nature. 1990 Apr 5;344(6266):549–552. doi: 10.1038/344549a0. [DOI] [PubMed] [Google Scholar]
  27. Moustacchi E., Enteric S. Differential "liquid holding recovery" for the lethal effect and cytoplasmic "petite" induction by UV light in Saccharomyces cerevisiae. Mol Gen Genet. 1970;109(1):69–83. doi: 10.1007/BF00334047. [DOI] [PubMed] [Google Scholar]
  28. Murray J. M., Carr A. M., Lehmann A. R., Watts F. Z. Cloning and characterisation of the rad9 DNA repair gene from Schizosaccharomyces pombe. Nucleic Acids Res. 1991 Jul 11;19(13):3525–3531. doi: 10.1093/nar/19.13.3525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nasim A., Smith B. P. Genetic control of radiation sensitivity in Schizosaccharomyces pombe. Genetics. 1975 Apr;79(4):573–582. doi: 10.1093/genetics/79.4.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Nasmyth K. A. Temperature-sensitive lethal mutants in the structural gene for DNA ligase in the yeast Schizosaccharomyces pombe. Cell. 1977 Dec;12(4):1109–1120. doi: 10.1016/0092-8674(77)90173-8. [DOI] [PubMed] [Google Scholar]
  31. Nurse P., Thuriaux P. Regulatory genes controlling mitosis in the fission yeast Schizosaccharomyces pombe. Genetics. 1980 Nov;96(3):627–637. doi: 10.1093/genetics/96.3.627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Phipps J., Nasim A., Miller D. R. Recovery, repair, and mutagenesis in Schizosaccharomyces pombe. Adv Genet. 1985;23:1–72. doi: 10.1016/s0065-2660(08)60511-8. [DOI] [PubMed] [Google Scholar]
  33. Rowley R. Repair of radiation-induced chromatid aberrations: relationship to G2 arrest in CHO cells. Int J Radiat Biol. 1990 Sep;58(3):489–498. doi: 10.1080/09553009014551831. [DOI] [PubMed] [Google Scholar]
  34. Russell P., Nurse P. Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog. Cell. 1987 May 22;49(4):559–567. doi: 10.1016/0092-8674(87)90458-2. [DOI] [PubMed] [Google Scholar]
  35. Russell P., Nurse P. The mitotic inducer nim1+ functions in a regulatory network of protein kinase homologs controlling the initiation of mitosis. Cell. 1987 May 22;49(4):569–576. doi: 10.1016/0092-8674(87)90459-4. [DOI] [PubMed] [Google Scholar]
  36. Russell P., Nurse P. cdc25+ functions as an inducer in the mitotic control of fission yeast. Cell. 1986 Apr 11;45(1):145–153. doi: 10.1016/0092-8674(86)90546-5. [DOI] [PubMed] [Google Scholar]
  37. Schmidt H., Kapitza-Fecke P., Stephen E. R., Gutz H. Some of the swi genes of Schizosaccharomyces pombe also have a function in the repair of radiation damage. Curr Genet. 1989 Aug;16(2):89–94. doi: 10.1007/BF00393400. [DOI] [PubMed] [Google Scholar]
  38. Shahin M. M., Gentner N. E., Nasim A. The effect of liquid holding in Schizosaccharomyces pombe strains after gamma and ultraviolet irradiation. Radiat Res. 1973 Feb;53(2):216–225. [PubMed] [Google Scholar]
  39. Simanis V., Nurse P. The cell cycle control gene cdc2+ of fission yeast encodes a protein kinase potentially regulated by phosphorylation. Cell. 1986 Apr 25;45(2):261–268. doi: 10.1016/0092-8674(86)90390-9. [DOI] [PubMed] [Google Scholar]
  40. Sinclair W. K. Cyclic x-ray responses in mammalian cells in vitro. Radiat Res. 1968 Mar;33(3):620–643. [PubMed] [Google Scholar]
  41. Strausfeld U., Labbé J. C., Fesquet D., Cavadore J. C., Picard A., Sadhu K., Russell P., Dorée M. Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 protein. Nature. 1991 May 16;351(6323):242–245. doi: 10.1038/351242a0. [DOI] [PubMed] [Google Scholar]
  42. Sunnerhagen P., Seaton B. L., Nasim A., Subramani S. Cloning and analysis of a gene involved in DNA repair and recombination, the rad1 gene of Schizosaccharomyces pombe. Mol Cell Biol. 1990 Jul;10(7):3750–3760. doi: 10.1128/mcb.10.7.3750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. WHITMORE G. F., STANNERS C. P., TILL J. E., GULYAS S. Nucleic acid synthesis and the division cycle in x-irradiated L-strain mouse cells. Biochim Biophys Acta. 1961 Feb 12;47:66–77. doi: 10.1016/0006-3002(61)90830-7. [DOI] [PubMed] [Google Scholar]
  44. Walters R. A., Gurley L. R., Tobey R. A. Effects of caffeine on radiation-induced phenomena associated with cell-cycle traverse of mammalian cells. Biophys J. 1974 Feb;14(2):99–118. doi: 10.1016/S0006-3495(74)70002-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Weibezahn K. F., Lohrer H., Herrlich P. Double-strand break repair and G2 block in Chinese hamster ovary cells and their radiosensitive mutants. Mutat Res. 1985 May;145(3):177–183. doi: 10.1016/0167-8817(85)90025-2. [DOI] [PubMed] [Google Scholar]
  46. Weinert T. A., Hartwell L. H. Characterization of RAD9 of Saccharomyces cerevisiae and evidence that its function acts posttranslationally in cell cycle arrest after DNA damage. Mol Cell Biol. 1990 Dec;10(12):6554–6564. doi: 10.1128/mcb.10.12.6554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Weinert T. A., Hartwell L. H. The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae. Science. 1988 Jul 15;241(4863):317–322. doi: 10.1126/science.3291120. [DOI] [PubMed] [Google Scholar]
  48. Weinert T., Hartwell L. Control of G2 delay by the rad9 gene of Saccharomyces cerevisiae. J Cell Sci Suppl. 1989;12:145–148. doi: 10.1242/jcs.1989.supplement_12.12. [DOI] [PubMed] [Google Scholar]
  49. Young P. G., Fantes P. A. Schizosaccharomyces pombe mutants affected in their division response to starvation. J Cell Sci. 1987 Oct;88(Pt 3):295–304. doi: 10.1242/jcs.88.3.295. [DOI] [PubMed] [Google Scholar]

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