Anatomy of a transcription factor important for the Start of the cell cycle in Saccharomyces cerevisiae

ENTRY of yeast cells into the mitotic cell cycle (Start) involves a form of the CDC28 kinase that associates with Gl-specific cyclins encoded by CLN1 and CLN2 (ref. 1). The onset of Start may be triggered by the activation of CLN1 and CLN2 transcription in late Gl (ref. 2). SWI4 and SWI6 are components of a factor (SBF) that binds the CACGAAAA (SCB) promoter elements3–5 responsible for activation in late Gl of the HO endonuclease, CLN1 and CLN2 genes6,7. A related factor (MBF) containing SWI6 and a 120K protein8 binds to the ACGCGTNA (MCB) promoter elements responsible for late Gl-specific transcription of DNA replication genes9–12. Nothing is known about how these heteromeric proteins bind DNA. We show here that SWI4 contains a novel DNA-binding domain at its N terminus that alone binds specifically to SCBs and a C-terminal domain that binds to SWI6. SWI4's DNA-binding domain is similar to an N-terminal domain of the cdclO protein that is a component of an MBF-like factor from Schizosaccharomyces pombe13 and is required for Start14,15. An involvement of this kind of DNA-binding domain in transcriptional controls at Start may therefore be a conserved feature of eukaryotic cells.

[1]  L. Breeden,et al.  Cell cycle-specific expression of the SWI4 transcription factor is required for the cell cycle regulation of HO transcription. , 1991, Genes & development.

[2]  K. Nasmyth,et al.  Changes in a SWI4,6-DNA-binding complex occur at the time of HO gene activation in yeast. , 1991, Genes & development.

[3]  Kim Nasmyth,et al.  Cell cycle control of the yeast HO gene: Cis- and Trans-acting regulators , 1987, Cell.

[4]  L. Johnston,et al.  Coordination of expression of DNA synthesis genes in budding yeast by a cell-cycle regulated trans factor , 1991, Nature.

[5]  L. Lanier,et al.  Co-association of CD3ζ with a receptor (CD16) for IgG Fc on human natural killer cells , 1989, Nature.

[6]  S. McKnight,et al.  Convergence of Ets- and notch-related structural motifs in a heteromeric DNA binding complex. , 1991, Science.

[7]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[8]  Samuel E. Lux,et al.  Analysis of cDNA for human erythrocyte ankyrin indicates a repeated structure with homology to tissue-differentiation and cell-cycle control proteins , 1990, Nature.

[9]  Kim Nasmyth,et al.  The role of SWI4 and SWI6 in the activity of G1 cyclins in yeast , 1991, Cell.

[10]  C. Gordon,et al.  A cell cycle-responsive transcriptional control element and a negative control element in the gene encoding DNA polymerase alpha in Saccharomyces cerevisiae. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[11]  P. Nurse,et al.  Gene required in G1 for commitment to cell cycle and in G2 for control of mitosis in fission yeast , 1981, Nature.

[12]  E. Wimmer,et al.  Synthesis of infectious poliovirus RNA by purified T7 RNA polymerase. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[13]  L. Johnston,et al.  Control of DNA synthesis genes in fission yeast by the cell-cycle gene cdclO + , 1992, Nature.

[14]  A T Bankier,et al.  Characterization of a transcription factor involved in mother cell specific transcription of the yeast HO gene. , 1988, The EMBO journal.

[15]  Curt Wittenberg,et al.  G1-specific cyclins of S. cerevisiae: Cell cycle periodicity, regulation by mating pheromone, and association with the p34 CDC28 protein kinase , 1990, Cell.

[16]  Brenda J. Andrews,et al.  Transcriptional activation of CLN1, CLN2, and a putative new G1 cyclin (HCS26) by SWI4, a positive regulator of G1-specific transcription , 1991, Cell.

[17]  W. Herr,et al.  A 100-kD HeLa cell octamer binding protein (OBP100) interacts differently with two separate octamer-related sequences within the SV40 enhancer. , 1987, Genes & development.

[18]  L. Breeden,et al.  Similarity between cell-cycle genes of budding yeast and fission yeast and the Notch gene of Drosophila , 1987, Nature.

[19]  J. Devereux,et al.  A comprehensive set of sequence analysis programs for the VAX , 1984, Nucleic Acids Res..

[20]  S. Aves,et al.  Cloning, sequencing and transcriptional control of the Schizosaccharomyces pombe cdc10 ‘start’ gene. , 1985, The EMBO journal.

[21]  Brenda J. Andrews,et al.  The yeast SWI4 protein contains a motif present in developmental regulators and is part of a complex involved in cell-cycle-dependent transcription , 1989, Nature.

[22]  Curt Wittenberg,et al.  An essential G1 function for cyclin-like proteins in yeast , 1989, Cell.

[23]  K. Nasmyth At least 1400 base pairs of 5′-flanking DNA is required for the correct expression of the HO gene in yeast , 1985, Cell.

[24]  Kim Nasmyth,et al.  A central role for SWI6 in modulating cell cycle Start-specific transcription in yeast , 1992, Nature.

[25]  G. Lucchini,et al.  DNA polymerase I gene of Saccharomyces cerevisiae: nucleotide sequence, mapping of a temperature-sensitive mutation, and protein homology with other DNA polymerases. , 1988, Proceedings of the National Academy of Sciences of the United States of America.