Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1994 Apr 15;13(8):1863–1872. doi: 10.1002/j.1460-2075.1994.tb06455.x

A B-type cyclin negatively regulates conjugation via interacting with cell cycle 'start' genes in fission yeast.

T Obara-Ishihara 1, H Okayama 1
PMCID: PMC395026  PMID: 7909513

Abstract

In the fission yeast Schizosaccharomyces pombe, the cdc10+/SWI family members constitute the cell cycle 'start' genes. res1+ and res2+ are the newly identified members of this family and encode putative association partners of the Cdc10 protein. The Pat1 kinase plays a pivotal role in switching between vegetative growth and sexual development, and its inactivation in haploid cells induces unconditional growth arrest and subsequent meiosis. We have identified as an extragenic suppressor of a temperature sensitive pat1-114 mutant, a new B-type cyclin that negatively regulates conjugation by interacting with these 'start' genes. This cyclin, named Cyc17, is highly homologous with Cdc13, but has no detectable activity as a mitotic cyclin. Deletion of cyc17+ markedly enhances conjugation, despite the presence of nitrogen source, and accelerates growth arrest in G1 upon nitrogen starvation. Conversely, overexpression of the cyc17+ gene strongly inhibits conjugation. The cyc17+ gene is transcribed into 3.2 kb poly(A)+ and 3.0 kb poly(A)- RNAs. Only the poly(A)+ species is expressed during vegetative growth and periodically with a peak in the G1 and S phases of the cell cycle. On the other hand, the poly(A)- transcript is highly induced during conjugation. This induction is lost in res2- cells, whereas the poly(A)+ transcript is significantly reduced in res1- cells. However, the mating inhibition as well as the ability to rescue the pat1 mutation by overexpression of res1+ and res2+ are totally abolished in cyc17- cells. Thus, in S.pombe, a B-type cyclin, regulated by the newly identified cell cycle 'start' genes, plays a crucial role in the control of sexual development.

Full text

PDF
1863

Images in this article

Selected References

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

  1. Andrews B. J., Herskowitz I. The yeast SWI4 protein contains a motif present in developmental regulators and is part of a complex involved in cell-cycle-dependent transcription. Nature. 1989 Dec 14;342(6251):830–833. doi: 10.1038/342830a0. [DOI] [PubMed] [Google Scholar]
  2. Aves S. J., Durkacz B. W., Carr A., Nurse P. Cloning, sequencing and transcriptional control of the Schizosaccharomyces pombe cdc10 'start' gene. EMBO J. 1985 Feb;4(2):457–463. doi: 10.1002/j.1460-2075.1985.tb03651.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Booher R., Beach D. Involvement of cdc13+ in mitotic control in Schizosaccharomyces pombe: possible interaction of the gene product with microtubules. EMBO J. 1988 Aug;7(8):2321–2327. doi: 10.1002/j.1460-2075.1988.tb03075.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Breeden L., Nasmyth K. Similarity between cell-cycle genes of budding yeast and fission yeast and the Notch gene of Drosophila. Nature. 1987 Oct 15;329(6140):651–654. doi: 10.1038/329651a0. [DOI] [PubMed] [Google Scholar]
  5. Bueno A., Richardson H., Reed S. I., Russell P. A fission yeast B-type cyclin functioning early in the cell cycle. Cell. 1991 Jul 12;66(1):149–159. doi: 10.1016/0092-8674(91)90147-q. [DOI] [PubMed] [Google Scholar]
  6. Bueno A., Russell P. Two fission yeast B-type cyclins, cig2 and Cdc13, have different functions in mitosis. Mol Cell Biol. 1993 Apr;13(4):2286–2297. doi: 10.1128/mcb.13.4.2286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bücking-Throm E., Duntze W., Hartwell L. H., Manney T. R. Reversible arrest of haploid yeast cells in the initiation of DNA synthesis by a diffusible sex factor. Exp Cell Res. 1973 Jan;76(1):99–110. doi: 10.1016/0014-4827(73)90424-2. [DOI] [PubMed] [Google Scholar]
  8. Caligiuri M., Beach D. Sct1 functions in partnership with Cdc10 in a transcription complex that activates cell cycle START and inhibits differentiation. Cell. 1993 Feb 26;72(4):607–619. doi: 10.1016/0092-8674(93)90079-6. [DOI] [PubMed] [Google Scholar]
  9. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cross F. R. Cell cycle arrest caused by CLN gene deficiency in Saccharomyces cerevisiae resembles START-I arrest and is independent of the mating-pheromone signalling pathway. Mol Cell Biol. 1990 Dec;10(12):6482–6490. doi: 10.1128/mcb.10.12.6482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cross F. R. DAF1, a mutant gene affecting size control, pheromone arrest, and cell cycle kinetics of Saccharomyces cerevisiae. Mol Cell Biol. 1988 Nov;8(11):4675–4684. doi: 10.1128/mcb.8.11.4675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dirick L., Nasmyth K. Positive feedback in the activation of G1 cyclins in yeast. Nature. 1991 Jun 27;351(6329):754–757. doi: 10.1038/351754a0. [DOI] [PubMed] [Google Scholar]
  13. Egel R., Egel-Mitani M. Premeiotic DNA synthesis in fission yeast. Exp Cell Res. 1974 Sep;88(1):127–134. doi: 10.1016/0014-4827(74)90626-0. [DOI] [PubMed] [Google Scholar]
  14. Egel R., Nielsen O., Weilguny D. Sexual differentiation in fission yeast. Trends Genet. 1990 Nov;6(11):369–373. doi: 10.1016/0168-9525(90)90279-f. [DOI] [PubMed] [Google Scholar]
  15. Forsburg S. L., Nurse P. Identification of a G1-type cyclin puc1+ in the fission yeast Schizosaccharomyces pombe. Nature. 1991 May 16;351(6323):245–248. doi: 10.1038/351245a0. [DOI] [PubMed] [Google Scholar]
  16. Gordon C. B., Fantes P. A. The cdc22 gene of Schizosaccharomyces pombe encodes a cell cycle-regulated transcript. EMBO J. 1986 Nov;5(11):2981–2985. doi: 10.1002/j.1460-2075.1986.tb04595.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Grimm C., Kohli J., Murray J., Maundrell K. Genetic engineering of Schizosaccharomyces pombe: a system for gene disruption and replacement using the ura4 gene as a selectable marker. Mol Gen Genet. 1988 Dec;215(1):81–86. doi: 10.1007/BF00331307. [DOI] [PubMed] [Google Scholar]
  18. Hadwiger J. A., Wittenberg C., Richardson H. E., de Barros Lopes M., Reed S. I. A family of cyclin homologs that control the G1 phase in yeast. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6255–6259. doi: 10.1073/pnas.86.16.6255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hagan I., Hayles J., Nurse P. Cloning and sequencing of the cyclin-related cdc13+ gene and a cytological study of its role in fission yeast mitosis. J Cell Sci. 1988 Dec;91(Pt 4):587–595. doi: 10.1242/jcs.91.4.587. [DOI] [PubMed] [Google Scholar]
  20. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  21. Hereford L. M., Hartwell L. H. Sequential gene function in the initiation of Saccharomyces cerevisiae DNA synthesis. J Mol Biol. 1974 Apr 15;84(3):445–461. doi: 10.1016/0022-2836(74)90451-3. [DOI] [PubMed] [Google Scholar]
  22. Hunt T. Cell biology. Destruction's our delight... Nature. 1991 Jan 10;349(6305):100–101. doi: 10.1038/349100a0. [DOI] [PubMed] [Google Scholar]
  23. Igarashi M., Nagata A., Jinno S., Suto K., Okayama H. Wee1(+)-like gene in human cells. Nature. 1991 Sep 5;353(6339):80–83. doi: 10.1038/353080a0. [DOI] [PubMed] [Google Scholar]
  24. Iino Y., Yamamoto M. Negative control for the initiation of meiosis in Schizosaccharomyces pombe. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2447–2451. doi: 10.1073/pnas.82.8.2447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jackson R. J., Standart N. Do the poly(A) tail and 3' untranslated region control mRNA translation? Cell. 1990 Jul 13;62(1):15–24. doi: 10.1016/0092-8674(90)90235-7. [DOI] [PubMed] [Google Scholar]
  26. Lis J., Wu C. Protein traffic on the heat shock promoter: parking, stalling, and trucking along. Cell. 1993 Jul 16;74(1):1–4. doi: 10.1016/0092-8674(93)90286-y. [DOI] [PubMed] [Google Scholar]
  27. Lowndes N. F., Johnson A. L., Johnston L. H. Coordination of expression of DNA synthesis genes in budding yeast by a cell-cycle regulated trans factor. Nature. 1991 Mar 21;350(6315):247–250. doi: 10.1038/350247a0. [DOI] [PubMed] [Google Scholar]
  28. MacNeill S. A., Creanor J., Nurse P. Isolation, characterisation and molecular cloning of new mutant alleles of the fission yeast p34cdc2+ protein kinase gene: identification of temperature-sensitive G2-arresting alleles. Mol Gen Genet. 1991 Sep;229(1):109–118. doi: 10.1007/BF00264219. [DOI] [PubMed] [Google Scholar]
  29. McLeod M., Beach D. A specific inhibitor of the ran1+ protein kinase regulates entry into meiosis in Schizosaccharomyces pombe. Nature. 1988 Apr 7;332(6164):509–514. doi: 10.1038/332509a0. [DOI] [PubMed] [Google Scholar]
  30. McLeod M., Stein M., Beach D. The product of the mei3+ gene, expressed under control of the mating-type locus, induces meiosis and sporulation in fission yeast. EMBO J. 1987 Mar;6(3):729–736. doi: 10.1002/j.1460-2075.1987.tb04814.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Merrill G. F., Morgan B. A., Lowndes N. F., Johnston L. H. DNA synthesis control in yeast: an evolutionarily conserved mechanism for regulating DNA synthesis genes? Bioessays. 1992 Dec;14(12):823–830. doi: 10.1002/bies.950141206. [DOI] [PubMed] [Google Scholar]
  32. Minshull J., Blow J. J., Hunt T. Translation of cyclin mRNA is necessary for extracts of activated xenopus eggs to enter mitosis. Cell. 1989 Mar 24;56(6):947–956. doi: 10.1016/0092-8674(89)90628-4. [DOI] [PubMed] [Google Scholar]
  33. Miyamoto M., Tanaka K., Okayama H. res2+, a new member of the cdc10+/SWI4 family, controls the 'start' of mitotic and meiotic cycles in fission yeast. EMBO J. 1994 Apr 15;13(8):1873–1880. doi: 10.1002/j.1460-2075.1994.tb06456.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Moreno S., Hayles J., Nurse P. Regulation of p34cdc2 protein kinase during mitosis. Cell. 1989 Jul 28;58(2):361–372. doi: 10.1016/0092-8674(89)90850-7. [DOI] [PubMed] [Google Scholar]
  35. Nagata A., Igarashi M., Jinno S., Suto K., Okayama H. An additional homolog of the fission yeast cdc25+ gene occurs in humans and is highly expressed in some cancer cells. New Biol. 1991 Oct;3(10):959–968. [PubMed] [Google Scholar]
  36. Nash R., Tokiwa G., Anand S., Erickson K., Futcher A. B. The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog. EMBO J. 1988 Dec 20;7(13):4335–4346. doi: 10.1002/j.1460-2075.1988.tb03332.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Nasmyth K., Dirick L. The role of SWI4 and SWI6 in the activity of G1 cyclins in yeast. Cell. 1991 Sep 6;66(5):995–1013. doi: 10.1016/0092-8674(91)90444-4. [DOI] [PubMed] [Google Scholar]
  38. Nurse P., Bissett Y. Gene required in G1 for commitment to cell cycle and in G2 for control of mitosis in fission yeast. Nature. 1981 Aug 6;292(5823):558–560. doi: 10.1038/292558a0. [DOI] [PubMed] [Google Scholar]
  39. Ogas J., Andrews B. J., Herskowitz I. Transcriptional activation of CLN1, CLN2, and a putative new G1 cyclin (HCS26) by SWI4, a positive regulator of G1-specific transcription. Cell. 1991 Sep 6;66(5):1015–1026. doi: 10.1016/0092-8674(91)90445-5. [DOI] [PubMed] [Google Scholar]
  40. Okayama H., Kawaichi M., Brownstein M., Lee F., Yokota T., Arai K. High-efficiency cloning of full-length cDNA; construction and screening of cDNA expression libraries for mammalian cells. Methods Enzymol. 1987;154:3–28. doi: 10.1016/0076-6879(87)54067-8. [DOI] [PubMed] [Google Scholar]
  41. Okazaki K., Okazaki N., Kume K., Jinno S., Tanaka K., Okayama H. High-frequency transformation method and library transducing vectors for cloning mammalian cDNAs by trans-complementation of Schizosaccharomyces pombe. Nucleic Acids Res. 1990 Nov 25;18(22):6485–6489. doi: 10.1093/nar/18.22.6485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Reed S. I., Wittenberg C. Mitotic role for the Cdc28 protein kinase of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5697–5701. doi: 10.1073/pnas.87.15.5697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Richardson H. E., Wittenberg C., Cross F., Reed S. I. An essential G1 function for cyclin-like proteins in yeast. Cell. 1989 Dec 22;59(6):1127–1133. doi: 10.1016/0092-8674(89)90768-x. [DOI] [PubMed] [Google Scholar]
  44. Rogers S., Wells R., Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. doi: 10.1126/science.2876518. [DOI] [PubMed] [Google Scholar]
  45. Sachs A., Wahle E. Poly(A) tail metabolism and function in eucaryotes. J Biol Chem. 1993 Nov 5;268(31):22955–22958. [PubMed] [Google Scholar]
  46. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sugimoto A., Iino Y., Maeda T., Watanabe Y., Yamamoto M. Schizosaccharomyces pombe ste11+ encodes a transcription factor with an HMG motif that is a critical regulator of sexual development. Genes Dev. 1991 Nov;5(11):1990–1999. doi: 10.1101/gad.5.11.1990. [DOI] [PubMed] [Google Scholar]
  48. Sugiyama A., Tanaka K., Okazaki K., Nojima H., Okayama H. A zinc finger protein controls the onset of premeiotic DNA synthesis of fission yeast in a Mei2-independent cascade. EMBO J. 1994 Apr 15;13(8):1881–1887. doi: 10.1002/j.1460-2075.1994.tb06457.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Tanaka K., Okazaki K., Okazaki N., Ueda T., Sugiyama A., Nojima H., Okayama H. A new cdc gene required for S phase entry of Schizosaccharomyces pombe encodes a protein similar to the cdc 10+ and SWI4 gene products. EMBO J. 1992 Dec;11(13):4923–4932. doi: 10.1002/j.1460-2075.1992.tb05599.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Thuriaux P., Sipiczki M., Fantes P. A. Genetical analysis of a sterile mutant by protoplast fusion in the fission yeast Schizosaccharomyces pombe. J Gen Microbiol. 1980 Feb;116(2):525–528. doi: 10.1099/00221287-116-2-525. [DOI] [PubMed] [Google Scholar]
  51. Watanabe Y., Lino Y., Furuhata K., Shimoda C., Yamamoto M. The S.pombe mei2 gene encoding a crucial molecule for commitment to meiosis is under the regulation of cAMP. EMBO J. 1988 Mar;7(3):761–767. doi: 10.1002/j.1460-2075.1988.tb02873.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Wilkinson L. E., Pringle J. R. Transient G1 arrest of S. cerevisiae cells of mating type alpha by a factor produced by cells of mating type a. Exp Cell Res. 1974 Nov;89(1):175–187. doi: 10.1016/0014-4827(74)90200-6. [DOI] [PubMed] [Google Scholar]
  53. Wittenberg C., Sugimoto K., Reed S. I. G1-specific cyclins of S. cerevisiae: cell cycle periodicity, regulation by mating pheromone, and association with the p34CDC28 protein kinase. Cell. 1990 Jul 27;62(2):225–237. doi: 10.1016/0092-8674(90)90361-h. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES