YEAST
VOL.
6: 231-243 (1990)
The Start Gene CDC28 and the Genetic Stability of Yeast A. B. DEVIN, T. YU. PROSVIROVA, V. T. PESHEKHONOV, 0.V. CHEPURNAYA*, M. E. SMIRNOVA,
N. A. KOLTOVAYAt, E. N. TROITSKAYAI A N D I. P. ARMAN
Institute of Molecular Genetics, U.S.S.R. Academy of Sciences, Ademician Kurchatov Sq., Moscow 123182, U.S.S.R. * B. P. Konstantinov Institute of Nuclear Physics, U.S.S.R.Academy of Sciences, Gatchina, Leningrad Region 188350, U.S.S.R. +Joint Institute for Nuclear Research, Dubna, Moscow Region 141980, U.S.S.R. +,A.N . Bach Institute of Biochemistry, U.S.S.R. Academy of Sciences, 33 Leninsky Prospekt, Moscow I 1 7071, U.S.S.R. Received 23 May 1989; revised 18 December 1989
The cdc28-srm mutation in Saccharomyces cerevisiae decreases spontaneous and induced mitochondria1 rhomutability and the mitotic stability of native chromosomes and recombinant circular minichromsomes. The effects of cdc28-srm on the genetic stability of cells support the hypothesis that links cell cycle regulation in yeast to changes in chromatin organization dependent on the start gene CDC28 (Hayles and Nurse, 1986). KEY WORDS - Saccharomyces cerevisiae; cell cycle regulation; CDC28 gene;
rho- mutation; chromosome loss; plasmid
maintenance.
of the cdc2', CDC28 and CDC2Hs proteins are 62-63% homologous to each other and contain the I t is important to study the regulation of eukaryotic characteristic conserved regions of protein kinases cell division because, inter alia, disturbances in this (Hindley and Phear, 1984; Lee and Nurse, 1987; regulation are closely linked to neoplastic trans- Lorincz and Reed, 1984; Nurse, 1985). Sequences formation. Two species often serve as model objects homologous to CDC2Hs have been found in the for such studies: the budding yeast Saccharomyces DNA of a dozen different vertebrate species (Spurr cerevisiae and the fission yeast Schizosaccharomyces et al., 1988). Apparently these genes, like cdc2' and pombe. CDC28, encode evolutionary variants of one and A yeast cell which has just entered a new division the same highly conserved protein that is involved in cycle can, before a certain time expires, conjugate the division cycle regulation of eukaryotic cells. with a cell of the opposite mating type or assume Immune complexes containing the cdc2+,CDC28 the quiescent state. The completion of the cycle and CDC2Hs gene products show protein kinase becomes inevitable only when the so-called con- activity in vitro (Draetta et al., 1987; Reed et trol steps (Hayles and Nurse, 1986; Pringle and al., 1985; Simanis and Nurse, 1986). It has been Hartwell, 1981; Simanis et al., 1987) have been suggested that the passage of yeast cells through the passed. The only known control step of the cell cycle control steps of the division cycle may depend on the in S . cerrvisiae is called 'start' (Hartwell et al., 1974). phosphorylation of the protein substrates by the The essential genes responsible for the control cdc2' and CDC28 protein kinases (Hayles and steps of the division cycle have been identified in the Nurse, 1986; Murray, 1987). two yeast species: cdc2+ in Sch. pombe (Nurse and The activation of proteins homologous to the Bissett, 1981; Nurse and Thuriaux, 1980; Nurse et cdc2' and CDC28 products seems to be a universal ul., 1976) and CDC28 in S. cerevisiae (Reed, 1980; element of the mechanisms that control the onset of Reid and Hartwell, 1977).These two genes are func- mitosis in eukaryotic cells (Dunphy et al., 1988; tionally interchangeable (Beach et al., 1982; Booher Gautier et al., 1988; Labbe et al., 1988; Murray and Beach, 1986). The human gene CDC2Hs that 1988). can complement the cdc- mutations in Sch. pombe Saccharomyces cells that cease multiplication has been identified and mapped (Lee and Nurse, arrest with a G, nuclear DNA content in a state 1987; Spurr et al., 1988). The amino acid sequences known as the stationary or Gophase. Gocells remain INTRODUCTION
0749-503)
VOL.
6: 231-243 (1990)
The Start Gene CDC28 and the Genetic Stability of Yeast A. B. DEVIN, T. YU. PROSVIROVA, V. T. PESHEKHONOV, 0.V. CHEPURNAYA*, M. E. SMIRNOVA,
N. A. KOLTOVAYAt, E. N. TROITSKAYAI A N D I. P. ARMAN
Institute of Molecular Genetics, U.S.S.R. Academy of Sciences, Ademician Kurchatov Sq., Moscow 123182, U.S.S.R. * B. P. Konstantinov Institute of Nuclear Physics, U.S.S.R.Academy of Sciences, Gatchina, Leningrad Region 188350, U.S.S.R. +Joint Institute for Nuclear Research, Dubna, Moscow Region 141980, U.S.S.R. +,A.N . Bach Institute of Biochemistry, U.S.S.R. Academy of Sciences, 33 Leninsky Prospekt, Moscow I 1 7071, U.S.S.R. Received 23 May 1989; revised 18 December 1989
The cdc28-srm mutation in Saccharomyces cerevisiae decreases spontaneous and induced mitochondria1 rhomutability and the mitotic stability of native chromosomes and recombinant circular minichromsomes. The effects of cdc28-srm on the genetic stability of cells support the hypothesis that links cell cycle regulation in yeast to changes in chromatin organization dependent on the start gene CDC28 (Hayles and Nurse, 1986). KEY WORDS - Saccharomyces cerevisiae; cell cycle regulation; CDC28 gene;
rho- mutation; chromosome loss; plasmid
maintenance.
of the cdc2', CDC28 and CDC2Hs proteins are 62-63% homologous to each other and contain the I t is important to study the regulation of eukaryotic characteristic conserved regions of protein kinases cell division because, inter alia, disturbances in this (Hindley and Phear, 1984; Lee and Nurse, 1987; regulation are closely linked to neoplastic trans- Lorincz and Reed, 1984; Nurse, 1985). Sequences formation. Two species often serve as model objects homologous to CDC2Hs have been found in the for such studies: the budding yeast Saccharomyces DNA of a dozen different vertebrate species (Spurr cerevisiae and the fission yeast Schizosaccharomyces et al., 1988). Apparently these genes, like cdc2' and pombe. CDC28, encode evolutionary variants of one and A yeast cell which has just entered a new division the same highly conserved protein that is involved in cycle can, before a certain time expires, conjugate the division cycle regulation of eukaryotic cells. with a cell of the opposite mating type or assume Immune complexes containing the cdc2+,CDC28 the quiescent state. The completion of the cycle and CDC2Hs gene products show protein kinase becomes inevitable only when the so-called con- activity in vitro (Draetta et al., 1987; Reed et trol steps (Hayles and Nurse, 1986; Pringle and al., 1985; Simanis and Nurse, 1986). It has been Hartwell, 1981; Simanis et al., 1987) have been suggested that the passage of yeast cells through the passed. The only known control step of the cell cycle control steps of the division cycle may depend on the in S . cerrvisiae is called 'start' (Hartwell et al., 1974). phosphorylation of the protein substrates by the The essential genes responsible for the control cdc2' and CDC28 protein kinases (Hayles and steps of the division cycle have been identified in the Nurse, 1986; Murray, 1987). two yeast species: cdc2+ in Sch. pombe (Nurse and The activation of proteins homologous to the Bissett, 1981; Nurse and Thuriaux, 1980; Nurse et cdc2' and CDC28 products seems to be a universal ul., 1976) and CDC28 in S. cerevisiae (Reed, 1980; element of the mechanisms that control the onset of Reid and Hartwell, 1977).These two genes are func- mitosis in eukaryotic cells (Dunphy et al., 1988; tionally interchangeable (Beach et al., 1982; Booher Gautier et al., 1988; Labbe et al., 1988; Murray and Beach, 1986). The human gene CDC2Hs that 1988). can complement the cdc- mutations in Sch. pombe Saccharomyces cells that cease multiplication has been identified and mapped (Lee and Nurse, arrest with a G, nuclear DNA content in a state 1987; Spurr et al., 1988). The amino acid sequences known as the stationary or Gophase. Gocells remain INTRODUCTION
0749-503)
