mcm5/cdc46-bob1 bypasses the requirement for the S phase activator Cdc7p.

Cdc7p is a protein kinase that is required for G1/S transition and initiation of DNA replication in Saccharomyces cerevisiae. The mechanisms whereby Cdc7p and its substrates exerts their effects are unknown. We report here the characterization in S. cerevisiae of a recessive mutation in a member of the MCM family, MCM5/CDC46, which bypasses the requirement for Cdc7p and its interacting factor Dbf4p. Because the MCM family of evolutionarily conserved proteins have been implicated in restricting DNA replication to once per cell cycle, our studies suggest that Cdc7p is required late in G1 because in its absence the Mcm5p/Cdc46p blocks the initiation of DNA replication. Moreover, Mcm5p/Cdc46p may have both positive and negative effects on the ability of cell to initiate replication.

[1]  B. Stillman,et al.  Cell Cycle Control of DNA Replication , 1996, Science.

[2]  A. Pautz,et al.  A novel role for Cdc5p in DNA replication , 1996, Molecular and cellular biology.

[3]  J. Blow,et al.  The Xenopus origin recognition complex is essential for DNA replication and MCM binding to chromatin , 1996, Current Biology.

[4]  J. Gautier,et al.  Phosphorylation of MCM4 by cdc2 protein kinase inhibits the activity of the minichromosome maintenance complex. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[5]  G. Evan,et al.  Interaction between the Origin Recognition Complex and the Replication Licensing Systemin Xenopus , 1996, Cell.

[6]  T. Coleman,et al.  The Xenopus Cdc6 Protein Is Essential for the Initiation of a Single Round of DNA Replication in Cell-Free Extracts , 1996, Cell.

[7]  R. Laskey,et al.  XMCM7, a novel member of the Xenopus MCM family, interacts with XMCM3 and colocalizes with it throughout replication. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[8]  C. F. Hardy.  Characterization of an essential Orc2p-associated factor that plays a role in DNA replication , 1996, Molecular and cellular biology.

[9]  M. Méchali,et al.  Chromotin binding, nuclear localization and phosphorylation of Xenopus cdc21 are cell‐cycle dependent and associated with the control of initiation of DNA replication. , 1996, The EMBO journal.

[10]  I. Todorov,et al.  The role of MCM proteins in the cell cycle control of genome duplication , 1996, BioEssays : news and reviews in molecular, cellular and developmental biology.

[11]  J. Blow,et al.  The role of MCM/P1 proteins in the licensing of DNA replication. , 1996, Trends in biochemical sciences.

[12]  R. Sclafani,et al.  Cell cycle regulation of induced mutagenesis in yeast. , 1995, Mutation research.

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

[14]  J. Rine,et al.  The origin recognition complex in silencing, cell cycle progression, and DNA replication. , 1995, Molecular biology of the cell.

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

[16]  R. Weinberg,et al.  The retinoblastoma protein and cell cycle control , 1995, Cell.

[17]  S. Dalton,et al.  Cell cycle-regulated nuclear import and export of Cdc47, a protein essential for initiation of DNA replication in budding yeast. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[18]  S. Dalton,et al.  Cdc54 belongs to the Cdc46/Mcm3 family of proteins which are essential for initiation of eukaryotic DNA replication. , 1995, Gene.

[19]  K. Sugimoto,et al.  DNA polymerase alpha associated protein P1, a murine homolog of yeast MCM3, changes its intranuclear distribution during the DNA synthetic period. , 1994, The EMBO journal.

[20]  J. Diffley,et al.  Interaction of Dbf4, the Cdc7 protein kinase regulatory subunit, with yeast replication origins in vivo. , 1994, Science.

[21]  J. Diffley,et al.  Two steps in the assembly of complexes at yeast replication origins in vivo , 1994, Cell.

[22]  C. Sherr.  The ins and outs of RB: coupling gene expression to the cell cycle clock. , 1994, Trends in cell biology.

[23]  J. Rine,et al.  Origin recognition complex (ORC) in transcriptional silencing and DNA replication in S. cerevisiae. , 1993, Science.

[24]  A. Jackson,et al.  Cell cycle regulation of the yeast Cdc7 protein kinase by association with the Dbf4 protein , 1993, Molecular and cellular biology.

[25]  H. Yoon,et al.  Regulation of Saccharomyces cerevisiae CDC7 function during the cell cycle. , 1993, Molecular biology of the cell.

[26]  D. Botstein,et al.  CDC46/MCM5, a yeast protein whose subcellular localization is cell cycle-regulated, is involved in DNA replication at autonomously replicating sequences. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[27]  B. Tye,et al.  Mcm2 and Mcm3, two proteins important for ARS activity, are related in structure and function. , 1991, Genes & development.

[28]  D. Botstein,et al.  A group of interacting yeast DNA replication genes. , 1991, Genes & development.

[29]  J. Rine,et al.  A role for CDC7 in repression of transcription at the silent mating-type locus HMR in Saccharomyces cerevisiae , 1991, Molecular and cellular biology.

[30]  D. Botstein,et al.  Subcellular localization of yeast CDC46 varies with the cell cycle. , 1990, Genes & development.

[31]  B. Tye,et al.  Mutants of S. cerevisiae defective in the maintenance of minichromosomes. , 1984, Genetics.

[32]  D. Botstein,et al.  Cold-sensitive cell-division-cycle mutants of yeast: isolation, properties, and pseudoreversion studies. , 1982, Genetics.

[33]  L. Hartwell,et al.  Sequential gene function in the initiation of Saccharomyces cerevisiae DNA synthesis. , 1974, Journal of molecular biology.

[34]  G. Simchen.  Are mitotic functions required in meiosis? , 1974, Genetics.