DNA replication in vertebrates requires a homolog of the Cdc7 protein kinase.

CDC7 is an essential gene required for DNA replication in Saccharomyces cerevisiae. Cdc7p homologs have recently been identified in vertebrates, but their role in DNA replication has not yet been addressed. Here we show that antibodies to the Xenopus laevis homolog, xCdc7, interfere with DNA replication in vivo in developing embryos and in vitro in cycling egg extracts. We also demonstrate cell cycle-dependent association of xCdc7 with the Mcm complex, which binds to replication origins and also is required for DNA synthesis. Taken together, these data indicate that the function of xCdc7 is conserved from fungi to vertebrates. xCdc7 protein accumulates after stimulation of resting oocytes with progesterone, suggesting a molecular explanation for previous observations that the development of the capacity for DNA replication requires protein synthesis late in meiosis I.

[1]  S. Forsburg,et al.  Schizosaccharomyces pombe Mcm3p, an essential nuclear protein, associates tightly with Nda4p (Mcm5p). , 1998, Nucleic acids research.

[2]  G. Wahl,et al.  Genetic dissection of a mammalian replicator in the human beta-globin locus. , 1998, Science.

[3]  S. Forsburg,et al.  Multiple domains of fission yeast Cdc19p (MCM2) are required for its association with the core MCM complex. , 1998, Molecular biology of the cell.

[4]  R. Hollingsworth,et al.  A human homolog of the yeast CDC7 gene is overexpressed in some tumors and transformed cell lines. , 1998, Gene.

[5]  J. Maller,et al.  Developmental regulation of MCM replication factors in Xenopus laevis , 1998, Current Biology.

[6]  W. L. Fangman,et al.  Cdc7 is required throughout the yeast S phase to activate replication origins. , 1998, Genes & development.

[7]  J. Diffley,et al.  The Cdc7 protein kinase is required for origin firing during S phase. , 1998, Genes & development.

[8]  T. Hunter,et al.  Identification and characterization of a human protein kinase related to budding yeast Cdc7p. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[9]  M. Lei,et al.  Mcm2 is a target of regulation by Cdc7-Dbf4 during the initiation of DNA synthesis. , 1997, Genes & development.

[10]  J. Bartek,et al.  The retinoblastoma protein pathway in cell cycle control and cancer. , 1997, Experimental cell research.

[11]  O. Aparicio,et al.  Components and Dynamics of DNA Replication Complexes in S. cerevisiae: Redistribution of MCM Proteins and Cdc45p during S Phase , 1997, Cell.

[12]  A. Lewellyn,et al.  A role for cyclin E/Cdk2 in the timing of the midblastula transition in Xenopus embryos. , 1997, Developmental biology.

[13]  K. Arai,et al.  Human and Xenopus cDNAs encoding budding yeast Cdc7‐related kinases: in vitro phosphorylation of MCM subunits by a putative human homologue of Cdc7 , 1997, The EMBO journal.

[14]  A. Lewellyn,et al.  Ionizing radiation induces apoptosis and elevates cyclin A1-Cdk2 activity before but not after the midblastula transition in Xenopus. , 1997, Molecular biology of the cell.

[15]  P. Pahl,et al.  mcm5/cdc46-bob1 bypasses the requirement for the S phase activator Cdc7p. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. Walter,et al.  Regulation of Replicon Size in Xenopus Egg Extracts , 1997, Science.

[17]  L. Johnston,et al.  Getting started: regulating the initiation of DNA replication in yeast. , 1997, Annual review of microbiology.

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

[19]  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.

[20]  K. Nasmyth.  At the heart of the budding yeast cell cycle. , 1996, Trends in genetics : TIG.

[21]  U. Strausfeld,et al.  Both cyclin A and cyclin E have S-phase promoting (SPF) activity in Xenopus egg extracts. , 1996, Journal of cell science.

[22]  A. Lewellyn,et al.  Mos proto-oncogene function during oocyte maturation in Xenopus. , 1996, Oncogene.

[23]  A. Futcher,et al.  Linkage of Replication to Start by the Cdk Inhibitor Sic1 , 1996, Science.

[24]  W. Dunphy,et al.  Role for a Xenopus Orc2-related protein in controlling DNA replication , 1996, Nature.

[25]  K. Nasmyth,et al.  An essential role for the Cdc6 protein in forming the pre-replicative complexes of budding yeast , 1996, Nature.

[26]  J. Marx.  Cell Division: How DNA Replication Originates , 1995, Science.

[27]  M. Méchali,et al.  Transition in Specification of Embryonic Metazoan DNA Replication Origins , 1995, Science.

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

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

[30]  S. Friend,et al.  E2F and its developmental regulation in Xenopus laevis , 1994, Molecular and cellular biology.

[31]  K. Okazaki,et al.  Suppression of DNA replication via Mos function during meiotic divisions in Xenopus oocytes. , 1994, The EMBO journal.

[32]  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.

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

[34]  K. Nasmyth,et al.  Yeast origin recognition complex is involved in DNA replication and transcriptional silencing , 1993, Nature.

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

[36]  Joel Moss,et al.  Rapid, reliable ligation-independent cloning of PCR products using modified plasmid vectors. , 1992, BioTechniques.

[37]  F. Cross,et al.  CLB5: a novel B cyclin from budding yeast with a role in S phase. , 1992, Genes & development.

[38]  Andrew W. Murray,et al.  Chapter 30 Cell Cycle Extracts , 1991 .

[39]  S. Hanks,et al.  Protein kinase catalytic domain sequence database: identification of conserved features of primary structure and classification of family members. , 1991, Methods in enzymology.

[40]  Jeremy Minshull,et al.  Cyclin is a component of maturation-promoting factor from Xenopus , 1990, Cell.

[41]  R. Benbow,et al.  Cytoplasmic control of nuclear DNA synthesis during early development of Xenopus laevis: a cell-free assay. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[42]  D. Hogness,et al.  The units of DNA replication in Drosophila melanogaster chromosomes. , 1974, Cold Spring Harbor symposia on quantitative biology.

[43]  R. Gesteland,et al.  Processing of Adenovirus 2-Induced Proteins , 1973, Journal of virology.

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

[45]  J. Gurdon,et al.  The appearance of cytoplasmic DNA polymerase activity during the maturation of amphibian oocytes into eggs. , 1969, Experimental cell research.

[46]  J. Gurdon.  On the origin and persistence of a cytoplasmic state inducing nuclear DNA synthesis in frogs' eggs. , 1967, Proceedings of the National Academy of Sciences of the United States of America.