Abstract
The Saccharomyces cerevisiae CLN3 protein, a G1 cyclin, positively regulates the expression of CLN1 and CLN2, two additional G1 cyclins whose expression during late G1 is activated, in part, by the transcription factors SWI4 and SWI6. We isolated 12 complementation groups of mutants that require CLN3. The members of one of these complementation groups have mutations in the BCK2 gene. In a wild-type CLN3 genetic background, bck2 mutants have a normal growth rate but have a larger cell size, are more sensitive to alpha-factor, and have a modest defect in the accumulation of CLN1 and CLN2 RNA. In the absence of CLN3, bck2 mutations cause an extremely slow growth rate: the cells accumulate in late G1 with very low levels of CLN1 and CLN2 RNA. The slow growth rate and long G1 delay of bck2 cln3 mutants are cured by heterologous expression of CLN2. Moreover, overexpression of BCK2 induces very high levels of CLN1, CLN2, and HCS26 RNAs. The results suggest that BCK2 and CLN3 provide parallel activation pathways for the expression of CLN1 and CLN2 during late G1.
Full Text
The Full Text of this article is available as a PDF (702.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andrews B. J., Herskowitz I. Identification of a DNA binding factor involved in cell-cycle control of the yeast HO gene. Cell. 1989 Apr 7;57(1):21–29. doi: 10.1016/0092-8674(89)90168-2. [DOI] [PubMed] [Google Scholar]
- 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]
- Andrews B. J., Moore L. A. Interaction of the yeast Swi4 and Swi6 cell cycle regulatory proteins in vitro. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11852–11856. doi: 10.1073/pnas.89.24.11852. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boeke J. D., Trueheart J., Natsoulis G., Fink G. R. 5-Fluoroorotic acid as a selective agent in yeast molecular genetics. Methods Enzymol. 1987;154:164–175. doi: 10.1016/0076-6879(87)54076-9. [DOI] [PubMed] [Google Scholar]
- Breeden L., Mikesell G. E. Cell cycle-specific expression of the SWI4 transcription factor is required for the cell cycle regulation of HO transcription. Genes Dev. 1991 Jul;5(7):1183–1190. doi: 10.1101/gad.5.7.1183. [DOI] [PubMed] [Google Scholar]
- Chang F., Herskowitz I. Identification of a gene necessary for cell cycle arrest by a negative growth factor of yeast: FAR1 is an inhibitor of a G1 cyclin, CLN2. Cell. 1990 Nov 30;63(5):999–1011. doi: 10.1016/0092-8674(90)90503-7. [DOI] [PubMed] [Google Scholar]
- Chang F., Herskowitz I. Phosphorylation of FAR1 in response to alpha-factor: a possible requirement for cell-cycle arrest. Mol Biol Cell. 1992 Apr;3(4):445–450. doi: 10.1091/mbc.3.4.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cross F. R., Blake C. M. The yeast Cln3 protein is an unstable activator of Cdc28. Mol Cell Biol. 1993 Jun;13(6):3266–3271. doi: 10.1128/mcb.13.6.3266. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Cross F. R., Hoek M., McKinney J. D., Tinkelenberg A. H. Role of Swi4 in cell cycle regulation of CLN2 expression. Mol Cell Biol. 1994 Jul;14(7):4779–4787. doi: 10.1128/mcb.14.7.4779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cross F. R., Tinkelenberg A. H. A potential positive feedback loop controlling CLN1 and CLN2 gene expression at the start of the yeast cell cycle. Cell. 1991 May 31;65(5):875–883. doi: 10.1016/0092-8674(91)90394-e. [DOI] [PubMed] [Google Scholar]
- Cvrcková F., Nasmyth K. Yeast G1 cyclins CLN1 and CLN2 and a GAP-like protein have a role in bud formation. EMBO J. 1993 Dec 15;12(13):5277–5286. doi: 10.1002/j.1460-2075.1993.tb06223.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Di Como C. J., Bose R., Arndt K. T. Overexpression of SIS2, which contains an extremely acidic region, increases the expression of SWI4, CLN1 and CLN2 in sit4 mutants. Genetics. 1995 Jan;139(1):95–107. doi: 10.1093/genetics/139.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dirick L., Moll T., Auer H., Nasmyth K. A central role for SWI6 in modulating cell cycle Start-specific transcription in yeast. Nature. 1992 Jun 11;357(6378):508–513. doi: 10.1038/357508a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Elledge S. J., Davis R. W. Two genes differentially regulated in the cell cycle and by DNA-damaging agents encode alternative regulatory subunits of ribonucleotide reductase. Genes Dev. 1990 May;4(5):740–751. doi: 10.1101/gad.4.5.740. [DOI] [PubMed] [Google Scholar]
- Epstein C. B., Cross F. R. CLB5: a novel B cyclin from budding yeast with a role in S phase. Genes Dev. 1992 Sep;6(9):1695–1706. doi: 10.1101/gad.6.9.1695. [DOI] [PubMed] [Google Scholar]
- Epstein C. B., Cross F. R. Genes that can bypass the CLN requirement for Saccharomyces cerevisiae cell cycle START. Mol Cell Biol. 1994 Mar;14(3):2041–2047. doi: 10.1128/mcb.14.3.2041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fernandez-Sarabia M. J., Sutton A., Zhong T., Arndt K. T. SIT4 protein phosphatase is required for the normal accumulation of SWI4, CLN1, CLN2, and HCS26 RNAs during late G1. Genes Dev. 1992 Dec;6(12A):2417–2428. doi: 10.1101/gad.6.12a.2417. [DOI] [PubMed] [Google Scholar]
- Fitch I., Dahmann C., Surana U., Amon A., Nasmyth K., Goetsch L., Byers B., Futcher B. Characterization of four B-type cyclin genes of the budding yeast Saccharomyces cerevisiae. Mol Biol Cell. 1992 Jul;3(7):805–818. doi: 10.1091/mbc.3.7.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Koch C., Moll T., Neuberg M., Ahorn H., Nasmyth K. A role for the transcription factors Mbp1 and Swi4 in progression from G1 to S phase. Science. 1993 Sep 17;261(5128):1551–1557. doi: 10.1126/science.8372350. [DOI] [PubMed] [Google Scholar]
- Kranz J. E., Holm C. Cloning by function: an alternative approach for identifying yeast homologs of genes from other organisms. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6629–6633. doi: 10.1073/pnas.87.17.6629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee K. S., Hines L. K., Levin D. E. A pair of functionally redundant yeast genes (PPZ1 and PPZ2) encoding type 1-related protein phosphatases function within the PKC1-mediated pathway. Mol Cell Biol. 1993 Sep;13(9):5843–5853. doi: 10.1128/mcb.13.9.5843. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lowndes N. F., Johnson A. L., Breeden L., Johnston L. H. SWI6 protein is required for transcription of the periodically expressed DNA synthesis genes in budding yeast. Nature. 1992 Jun 11;357(6378):505–508. doi: 10.1038/357505a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Moll T., Dirick L., Auer H., Bonkovsky J., Nasmyth K. SWI6 is a regulatory subunit of two different cell cycle START-dependent transcription factors in Saccharomyces cerevisiae. J Cell Sci Suppl. 1992;16:87–96. doi: 10.1242/jcs.1992.supplement_16.11. [DOI] [PubMed] [Google Scholar]
- Nagawa F., Fink G. R. The relationship between the "TATA" sequence and transcription initiation sites at the HIS4 gene of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8557–8561. doi: 10.1073/pnas.82.24.8557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- Richardson H., Lew D. J., Henze M., Sugimoto K., Reed S. I. Cyclin-B homologs in Saccharomyces cerevisiae function in S phase and in G2. Genes Dev. 1992 Nov;6(11):2021–2034. doi: 10.1101/gad.6.11.2021. [DOI] [PubMed] [Google Scholar]
- Rose M. D., Novick P., Thomas J. H., Botstein D., Fink G. R. A Saccharomyces cerevisiae genomic plasmid bank based on a centromere-containing shuttle vector. Gene. 1987;60(2-3):237–243. doi: 10.1016/0378-1119(87)90232-0. [DOI] [PubMed] [Google Scholar]
- Stuart D., Wittenberg C. Cell cycle-dependent transcription of CLN2 is conferred by multiple distinct cis-acting regulatory elements. Mol Cell Biol. 1994 Jul;14(7):4788–4801. doi: 10.1128/mcb.14.7.4788. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sutton A., Immanuel D., Arndt K. T. The SIT4 protein phosphatase functions in late G1 for progression into S phase. Mol Cell Biol. 1991 Apr;11(4):2133–2148. doi: 10.1128/mcb.11.4.2133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taba M. R., Muroff I., Lydall D., Tebb G., Nasmyth K. Changes in a SWI4,6-DNA-binding complex occur at the time of HO gene activation in yeast. Genes Dev. 1991 Nov;5(11):2000–2013. doi: 10.1101/gad.5.11.2000. [DOI] [PubMed] [Google Scholar]
- Tyers M., Tokiwa G., Futcher B. Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins. EMBO J. 1993 May;12(5):1955–1968. doi: 10.1002/j.1460-2075.1993.tb05845.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tyers M., Tokiwa G., Nash R., Futcher B. The Cln3-Cdc28 kinase complex of S. cerevisiae is regulated by proteolysis and phosphorylation. EMBO J. 1992 May;11(5):1773–1784. doi: 10.1002/j.1460-2075.1992.tb05229.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Verma R., Smiley J., Andrews B., Campbell J. L. Regulation of the yeast DNA replication genes through the Mlu I cell cycle box is dependent on SWI6. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9479–9483. doi: 10.1073/pnas.89.20.9479. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]