p25rum1 orders S phase and mitosis by acting as an inhibitor of the p34cdc2 mitotic kinase

p25rum1 from the fission yeast S. pombe is shown to act as a specific in vitro inhibitor of the p34cdc2/p56cdc13 mitotic kinase. It is also shown that early G1 cells contain p25rum1, which associates with and inhibits the mitotic kinase, and maintains p56cdc13 mitotic B cyclin at a low level, ensuring that these cells do not undergo a premature lethal entry into mitosis. A high level of p25rum1 in G2 cells inhibits the p34cdc2/p56cdc13 kinase that removes the block preventing a further S phase and leads to repeated rounds of DNA replication. Thus, the cyclin-dependent kinase inhibitor p25rum1, acting on the p34cdc2 mitotic kinase, plays an important role in ensuring the correct sequence of S phase and mitosis during the cell cycle.

[1]  Kathleen L. Gould,et al.  Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis , 1989, Nature.

[2]  P. Nurse,et al.  A single fission yeast mitotic cyclin B p34cdc2 kinase promotes both S‐phase and mitosis in the absence of G1 cyclins. , 1996, The EMBO journal.

[3]  Mike Tyers,et al.  Mechanisms that help the yeast cell cycle clock tick: G2 cyclins transcriptionally activate G2 cyclins and repress G1 cyclins , 1993, Cell.

[4]  R. Laskey,et al.  MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells , 1995, Nature.

[5]  H. Okayama,et al.  A B‐type cyclin negatively regulates conjugation via interacting with cell cycle ‘start’ genes in fission yeast. , 1994, The EMBO journal.

[6]  M. Yanagida,et al.  Bypassing anaphase by fission yeast cut9 mutation: requirement of cut9+ to initiate anaphase , 1994, The Journal of cell biology.

[7]  M. Mendenhall,et al.  An inhibitor of p34CDC28 protein kinase activity from Saccharomyces cerevisiae. , 1993, Science.

[8]  I. Herskowitz,et al.  Direct inhibition of the yeast cyclin-dependent kinase Cdc28-Cln by Far1. , 1994, Science.

[9]  Stuart Tugendreich,et al.  CDC27Hs colocalizes with CDC16Hs to the centrosome and mitotic spindle and is essential for the metaphase to anaphase transition , 1995, Cell.

[10]  C. Lehner,et al.  Distinct modes of cyclin E/cdc2c kinase regulation and S-phase control in mitotic and endoreduplication cycles of Drosophila embryogenesis. , 1995, Genes & development.

[11]  M. Kirschner,et al.  Mitosis in transition , 1994, Cell.

[12]  M. Yanagida,et al.  A temperature-sensitive mutation of the Schizosaccharomyces pombe gene nuc2+ that encodes a nuclear scaffold-like protein blocks spindle elongation in mitotic anaphase , 1988, The Journal of cell biology.

[13]  Kim Nasmyth,et al.  The B-type cyclin kinase inhibitor p40 SIC1 controls the G1 to S transition in S. cerevisiae , 1994, Cell.

[14]  D. Beach,et al.  The fission yeast cdc2/cdc13/suc1 protein kinase: Regulation of catalytic activity and nuclear localization , 1989, Cell.

[15]  K Nasmyth,et al.  Control of the yeast cell cycle by the Cdc28 protein kinase. , 1993, Current opinion in cell biology.

[16]  P. Russell,et al.  A fission yeast B-type cyclin functioning early in the cell cycle , 1991, Cell.

[17]  D. Beach,et al.  Interaction between the Cig1 and Cig2 B-type cyclins in the fission yeast cell cycle , 1994, Molecular and cellular biology.

[18]  J. Hayles,et al.  A pre‐start checkpoint preventing mitosis in fission yeast acts independently of p34cdc2 tyrosine phosphorylation. , 1995, The EMBO journal.

[19]  P. O’Farrell,et al.  Qualifying for the license to replicate , 1995, Cell.

[20]  P. Nurse Universal control mechanism regulating onset of M-phase , 1990, Nature.

[21]  I. Herskowitz,et al.  Joining the complex: Cyclin-dependent kinase inhibitory proteins and the cell cycle , 1994, Cell.

[22]  S. Forsburg,et al.  The fission yeast cdc18 + gene product couples S phase to START and mitosis , 1993, Cell.

[23]  S. Moreno,et al.  Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. , 1991, Methods in enzymology.

[24]  James M. Roberts,et al.  Inhibitors of mammalian G1 cyclin-dependent kinases. , 1995, Genes & development.

[25]  E. Nigg,et al.  Cyclin‐dependent protein kinases: Key regulators of the eukaryotic cell cycle , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.

[26]  L. Johnston,et al.  P40SDB25, a putative CDK inhibitor, has a role in the M/G1 transition in Saccharomyces cerevisiae. , 1994, Genes & development.

[27]  S. Moreno,et al.  Regulation of progression through the G1 phase of the cell cycle by the rum1+ gene , 1994 .

[28]  M. Mendenhall,et al.  An inhibitor of yeast cyclin-dependent protein kinase plays an important role in ensuring the genomic integrity of daughter cells. , 1994, Molecular and cellular biology.

[29]  Sergio Moreno,et al.  Regulation of p34cdc2 protein kinase during mitosis , 1989, Cell.

[30]  E. Nigg,et al.  Differential phosphorylation of vertebrate p34cdc2 kinase at the G1/S and G2/M transitions of the cell cycle: identification of major phosphorylation sites. , 1991, The EMBO journal.

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

[32]  Kim Nasmyth,et al.  Genes involved in sister chromatid separation are needed for b-type cyclin proteolysis in budding yeast , 1995, Cell.

[33]  G. Draetta,et al.  p13suc1 of Schizosaccharomyces pombe regulates two distinct forms of the mitotic cdc2 kinase , 1995, Molecular and cellular biology.

[34]  P. Nurse,et al.  The cell cycle control gene cdc2 + of fission yeast encodes a protein kinase potentially regulated by phosphorylation , 1986, Cell.

[35]  M. Kirschner,et al.  A 20s complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B , 1995, Cell.

[36]  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.

[37]  U. K. Laemmli,et al.  Study of the cell cycle‐dependent assembly of the DNA pre‐replication centres in Xenopus egg extracts. , 1994, The EMBO journal.

[38]  P. Russell,et al.  Two Fission Yeast B-Type Cyclins, Cig2 and Cdc13, Have Different Functions in Mitosis , 1993, Molecular and cellular biology.

[39]  P. Nurse,et al.  Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates. , 1991, The EMBO journal.

[40]  J. Hayles,et al.  Temporal order of S phase and mitosis in fission yeast is determined by the state of the p34 cdc2 -mitotic B cyclin complex , 1994, Cell.

[41]  K Nasmyth,et al.  CLB5 and CLB6, a new pair of B cyclins involved in DNA replication in Saccharomyces cerevisiae. , 1993, Genes & development.

[42]  H. Nojima,et al.  Identification of the yeast MCM3-related protein as a component of xenopus DNA replication licensing factor , 1995, Cell.

[43]  Karen Lundgren,et al.  mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2 , 1991, Cell.

[44]  James P. J. Chong,et al.  Purification of an MCM-containing complex as a component of the DNA replication licensing system , 1995, Nature.