![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
1 Section of Biochemistry, Molecular and Cell Biology,
Cornell University, Ithaca, New York 14853-2703 USA;
2 Research Institute for Microbial Diseases, Osaka University,
Osaka 565, Japan
The initiation of DNA synthesis is an important cell cycle event
that defines the beginning of S phase. This critical event involves the
participation of proteins whose functions are regulated by cyclin
dependent protein kinases (Cdks). The Mcm2-7 proteins are a family of
six conserved proteins that are essential for the initiation of DNA
synthesis in all eukaryotes. In Saccharomyces cerevisiae,
members of the Mcm2-7 family undergo cell cycle-specific phosphorylation. Phosphorylation of Mcm proteins at the beginning of S
phase coincides with the removal of these proteins from chromatin and
the onset of DNA synthesis. In this study, we identified DBF4, which encodes the regulatory subunit of a Cdk-like protein kinase Cdc7-Dbf4, in a screen for second site suppressors of mcm2-1. The dbf4 suppressor mutation restores competence to initiate
DNA synthesis to the mcm2-1 mutant. Cdc7-Dbf4 interacts
physically with Mcm2 and phosphorylates Mcm2 and three other members of
the Mcm2-7 family in vitro. Blocking the kinase activity of Cdc7-Dbf4 at the G1-to-S phase transition also blocks the
phosphorylation of Mcm2 at this defined point of the cell cycle. Taken
together, our data suggest that phosphorylation of Mcm2 and probably
other members of the Mcm2-7 proteins by Cdc7-Dbf4 at the
G1-to-S phase transition is a critical step in the initiation
of DNA synthesis at replication origins.
[Key Words: DNA replication; Mcm proteins; Cdc7-Dbf4 kinase]
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. L. Bochman and A. Schwacha Differences in the Single-stranded DNA Binding Activities of MCM2-7 and MCM467: MCM2 AND MCM5 DEFINE A SLOW ATP-DEPENDENT STEP J. Biol. Chem., November 16, 2007; 282(46): 33795 - 33804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Kim, S.-Y. Kim, and H. Lee Identification and Characterization of Human Cdc7 Nuclear Retention and Export Sequences in the Context of Chromatin Binding J. Biol. Chem., October 12, 2007; 282(41): 30029 - 30038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. P. Heffernan, K. Unsal-Kacmaz, A. N. Heinloth, D. A. Simpson, R. S. Paules, A. Sancar, M. Cordeiro-Stone, and W. K. Kaufmann Cdc7-Dbf4 and the Human S Checkpoint Response to UVC J. Biol. Chem., March 30, 2007; 282(13): 9458 - 9468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chattopadhyay, E. Tracy, P. Liang, O. Robledo, S. Rose-John, and H. Baumann Interleukin-31 and Oncostatin-M Mediate Distinct Signaling Reactions and Response Patterns in Lung Epithelial Cells J. Biol. Chem., February 2, 2007; 282(5): 3014 - 3026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Tenca, D. Brotherton, A. Montagnoli, S. Rainoldi, C. Albanese, and C. Santocanale Cdc7 Is an Active Kinase in Human Cancer Cells Undergoing Replication Stress J. Biol. Chem., January 5, 2007; 282(1): 208 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Masai, C. Taniyama, K. Ogino, E. Matsui, N. Kakusho, S. Matsumoto, J.-M. Kim, A. Ishii, T. Tanaka, T. Kobayashi, et al. Phosphorylation of MCM4 by Cdc7 Kinase Facilitates Its Interaction with Cdc45 on the Chromatin J. Biol. Chem., December 22, 2006; 281(51): 39249 - 39261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tsuji, S. B. Ficarro, and W. Jiang Essential Role of Phosphorylation of MCM2 by Cdc7/Dbf4 in the Initiation of DNA Replication in Mammalian Cells Mol. Biol. Cell, October 1, 2006; 17(10): 4459 - 4472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Dohrmann and R. A. Sclafani Novel Role for Checkpoint Rad53 Protein Kinase in the Initiation of Chromosomal DNA Replication in Saccharomyces cerevisiae Genetics, September 1, 2006; 174(1): 87 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fien and J. Hurwitz Fission Yeast Mcm10p Contains Primase Activity J. Biol. Chem., August 4, 2006; 281(31): 22248 - 22260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-H. Cho, Y.-J. Lee, S.-I. Kong, J. Hurwitz, and J.-K. Lee CDC7 kinase phosphorylates serine residues adjacent to acidic amino acids in the minichromosome maintenance 2 protein PNAS, August 1, 2006; 103(31): 11521 - 11526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Ricke and A.-K. Bielinsky A Conserved Hsp10-like Domain in Mcm10 Is Required to Stabilize the Catalytic Subunit of DNA Polymerase-{alpha} in Budding Yeast J. Biol. Chem., July 7, 2006; 281(27): 18414 - 18425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Moyer, P. W. Lewis, and M. R. Botchan Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase PNAS, July 5, 2006; 103(27): 10236 - 10241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Gabrielse, C. T. Miller, K. H. McConnell, A. DeWard, C. A. Fox, and M. Weinreich A Dbf4p BRCA1 C-Terminal-Like Domain Required for the Response to Replication Fork Arrest in Budding Yeast Genetics, June 1, 2006; 173(2): 541 - 555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ryu, J. Holzschuh, S. Erhardt, A.-K. Ettl, and W. Driever Depletion of minichromosome maintenance protein 5 in the zebrafish retina causes cell-cycle defect and apoptosis PNAS, December 20, 2005; 102(51): 18467 - 18472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. S. Takahashi and J. C. Walter Cdc7-Drf1 is a developmentally regulated protein kinase required for the initiation of vertebrate DNA replication Genes & Dev., October 1, 2005; 19(19): 2295 - 2300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Varrin, A. A. Prasad, R.-P. Scholz, M. D. Ramer, and B. P. Duncker A Mutation in Dbf4 Motif M Impairs Interactions with DNA Replication Factors and Confers Increased Resistance to Genotoxic Agents Mol. Cell. Biol., September 1, 2005; 25(17): 7494 - 7504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Yamashita, J.-M. Kim, O. Koiwai, K.-i. Arai, and H. Masai Functional analyses of mouse ASK, an activation subunit for Cdc7 kinase, using conditional ASK knockout ES cells Genes Cells, June 1, 2005; 10(6): 551 - 563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Nieduszynski, J. J. Blow, and A. D. Donaldson The requirement of yeast replication origins for pre-replication complex proteins is modulated by transcription Nucleic Acids Res., April 28, 2005; 33(8): 2410 - 2420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Tsvetkov and D. F. Stern Interaction of Chromatin-associated Plk1 and Mcm7 J. Biol. Chem., March 25, 2005; 280(12): 11943 - 11947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Williams and J. R. McIntosh Mcl1p Is a Polymerase {alpha} Replication Accessory Factor Important for S-Phase DNA Damage Survival Eukaryot. Cell, January 1, 2005; 4(1): 166 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Thomer, N. R. May, B. D. Aggarwal, G. Kwok, and B. R. Calvi Drosophila double-parked is sufficient to induce re-replication during development and is regulated by cyclin E/CDK2 Development, October 1, 2004; 131(19): 4807 - 4818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Pike, N. Tenis, and J. Heierhorst Rad53 Kinase Activation-independent Replication Checkpoint Function of the N-terminal Forkhead-associated (FHA1) Domain J. Biol. Chem., September 17, 2004; 279(38): 39636 - 39644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Forsburg Eukaryotic MCM Proteins: Beyond Replication Initiation Microbiol. Mol. Biol. Rev., March 1, 2004; 68(1): 109 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Yanow, D. A. Gold, H. Y. Yoo, and W. G. Dunphy Xenopus Drf1, a Regulator of Cdc7, Displays Checkpoint-dependent Accumulation on Chromatin during an S-phase Arrest J. Biol. Chem., October 17, 2003; 278(42): 41083 - 41092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Furukohri, N. Sato, H. Masai, K.-i. Arai, A. Sugino, and S. Waga Identification and Characterization of a Xenopus Homolog of Dbf4, a Regulatory Subunit of the Cdc7 Protein Kinase Required for the Initiation of DNA Replication J. Biochem., September 1, 2003; 134(3): 447 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Eide, K. A. Tasken, C. Carlson, G. Williams, T. Jahnsen, K. Tasken, and P. Collas Protein Kinase A-anchoring Protein AKAP95 Interacts with MCM2, a Regulator of DNA Replication J. Biol. Chem., July 11, 2003; 278(29): 26750 - 26756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Gladden and J. A. Diehl The Cyclin D1-dependent Kinase Associates with the Pre-replication Complex and Modulates RB{middle dot}MCM7 Binding J. Biol. Chem., March 7, 2003; 278(11): 9754 - 9760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. P. Duncker, K. Shimada, M. Tsai-Pflugfelder, P. Pasero, and S. M. Gasser An N-terminal domain of Dbf4p mediates interaction with both origin recognition complex (ORC) and Rad53p and can deregulate late origin firing PNAS, December 10, 2002; 99(25): 16087 - 16092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Claycomb, D. M. MacAlpine, J. G. Evans, S. P. Bell, and T. L. Orr-Weaver Visualization of replication initiation and elongation in Drosophila J. Cell Biol., October 28, 2002; 159(2): 225 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. H. Cheng, L. A. Roberts, and B. K. Tye Mcm3 Is Polyubiquitinated during Mitosis before Establishment of the Pre-replication Complex J. Biol. Chem., October 25, 2002; 277(44): 41706 - 41714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Chou, P. Petersen, J. C. Walter, and G. Walter Protein Phosphatase 2A Regulates Binding of Cdc45 to the Prereplication Complex J. Biol. Chem., October 18, 2002; 277(43): 40520 - 40527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lei, I. H. Cheng, L. A. Roberts, M. A. McAlear, and B. K. Tye Two mcm3 Mutations Affect Different Steps in the Initiation of DNA Replication J. Biol. Chem., August 16, 2002; 277(34): 30824 - 30831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Fung, J. Ou, S. Bueler, and G. W. Brown A Conserved Domain of Schizosaccharomyces pombe dfp1+ Is Uniquely Required for Chromosome Stability following Alkylation Damage during S Phase Mol. Cell. Biol., July 1, 2002; 22(13): 4477 - 4490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Garber and J. Rine Overlapping Roles of the Spindle Assembly and DNA Damage Checkpoints in the Cell-Cycle Response to Altered Chromosomes in Saccharomyces cerevisiae Genetics, June 1, 2002; 161(2): 521 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Angeletti, K. Kim, F. J. Fernandes, and P. F. Lambert Stable Replication of Papillomavirus Genomes in Saccharomyces cerevisiae J. Virol., March 7, 2002; 76(7): 3350 - 3358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Schwed, N. May, Y. Pechersky, and B. R. Calvi Drosophila Minichromosome Maintenance 6 Is Required for Chorion Gene Amplification and Genomic Replication Mol. Biol. Cell, February 1, 2002; 13(2): 607 - 620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakamura, M. Nakamura-Kubo, T. Nakamura, and C. Shimoda Novel Fission Yeast Cdc7-Dbf4-Like Kinase Complex Required for the Initiation and Progression of Meiotic Second Division Mol. Cell. Biol., January 1, 2002; 22(1): 309 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. EL-Gazzar, K. Maeda, H. Nomiyama, M. Nakao, K. Kuwahara, and N. Sakaguchi PU.1 Is Involved in the Regulation of B Lineage-associated and Developmental Stage-dependent Expression of the Germinal Center-associated DNA Primase GANP J. Biol. Chem., December 14, 2001; 276(51): 48000 - 48008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ishimi, Y. Komamura-Kohno, K.-i. Arai, and H. Masai Biochemical Activities Associated with Mouse Mcm2 Protein J. Biol. Chem., November 9, 2001; 276(46): 42744 - 42752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Weinreich, C. Liang, H.-H. Chen, and B. Stillman Inaugural Article: Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle PNAS, September 25, 2001; 98(20): 11211 - 11217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Takeda, K. Ogino, K. Tatebayashi, H. Ikeda, K.-i. Arai, and H. Masai Regulation of Initiation of S Phase, Replication Checkpoint Signaling, and Maintenance of Mitotic Chromosome Structures during S Phase by Hsk1 Kinase in the Fission Yeast Mol. Biol. Cell, May 1, 2001; 12(5): 1257 - 1274. [Abstract] [Full Text]
|
|
|
|
|
|
L. Lu, H. Zhang, and J. Tower Functionally distinct, sequence-specific replicator and origin elements are required for Drosophila chorion gene amplification Genes & Dev., January 15, 2001; 15(2): 134 - 146. [Abstract] [Full Text]
|
|
|
|
 |
|
 M Lei and B. Tye Initiating DNA synthesis: from recruiting to activating the MCM complex J. Cell Sci., January 4, 2001; 114(8): 1447 - 1454. [Abstract] [PDF]
|
|
|
|
|
|
J.-K. Lee and J. Hurwitz Processive DNA helicase activity of the minichromosome maintenance proteins 4, 6, and 7 complex requires forked DNA structures PNAS, January 2, 2001; 98(1): 54 - 59. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Snaith, G. W. Brown, and S. L. Forsburg Schizosaccharomyces pombe Hsk1p Is a Potential Cds1p Target Required for Genome Integrity Mol. Cell. Biol., November 1, 2000; 20(21): 7922 - 7932. [Abstract] [Full Text]
|
|
|
|
|
|
P. Jares and J. J. Blow Xenopus Cdc7 function is dependent on licensing but not on XORC, XCdc6, or CDK activity and is required for XCdc45 loading Genes & Dev., June 15, 2000; 14(12): 1528 - 1540. [Abstract] [Full Text]
|
|
|
|
|
|
R. Nougarède, F. Della Seta, P. Zarzov, and E. Schwob Hierarchy of S-Phase-Promoting Factors: Yeast Dbf4-Cdc7 Kinase Requires Prior S-Phase Cyclin-Dependent Kinase Activation Mol. Cell. Biol., June 1, 2000; 20(11): 3795 - 3806. [Abstract] [Full Text]
|
|
|
|
|
|
I. Pereverzeva, E. Whitmire, B. Khan, and M. Coué Distinct Phosphoisoforms of the Xenopus Mcm4 Protein Regulate the Function of the Mcm Complex Mol. Cell. Biol., May 15, 2000; 20(10): 3667 - 3676. [Abstract] [Full Text]
|
|
|
|
|
|
L. Zou and B. Stillman Assembly of a Complex Containing Cdc45p, Replication Protein A, and Mcm2p at Replication Origins Controlled by S-Phase Cyclin-Dependent Kinases and Cdc7p-Dbf4p Kinase Mol. Cell. Biol., May 1, 2000; 20(9): 3086 - 3096. [Abstract] [Full Text]
|
|
|
|
|
|
L. Homesley, M. Lei, Y. Kawasaki, S. Sawyer, T. Christensen, and B. K. Tye Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins Genes & Dev., April 15, 2000; 14(8): 913 - 926. [Abstract] [Full Text]
|
|
|
|
|
|
B. K. Tye From the Cover: Insights into DNA replication from the third domain of life PNAS, March 14, 2000; 97(6): 2399 - 2401. [Full Text] [PDF]
|
|
|
|
|
|
Y. Arata, M. Fujita, K. Ohtani, S. Kijima, and J.-y. Kato Cdk2-dependent and -independent Pathways in E2F-mediated S Phase Induction J. Biol. Chem., February 25, 2000; 275(9): 6337 - 6345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sclafani Cdc7p-Dbf4p becomes famous in the cell cycle J. Cell Sci., January 6, 2000; 113(12): 2111 - 2117. [Abstract] [PDF]
|
|
|
|
|
|
M. Godinho Ferreira, C. Santocanale, L. S. Drury, and J. F. X. Diffley Dbf4p, an Essential S Phase-Promoting Factor, Is Targeted for Degradation by the Anaphase-Promoting Complex Mol. Cell. Biol., January 1, 2000; 20(1): 242 - 248. [Abstract] [Full Text]
|
|
|
|
|
|
Z. You, Y. Komamura, and Y. Ishimi Biochemical Analysis of the Intrinsic Mcm4-Mcm6-Mcm7 DNA Helicase Activity Mol. Cell. Biol., December 1, 1999; 19(12): 8003 - 8015. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Pasero, B. P. Duncker, E. Schwob, and S. M. Gasser A role for the Cdc7 kinase regulatory subunit Dbf4p in the formation of initiation-competent origins of replication Genes & Dev., August 15, 1999; 13(16): 2159 - 2176. [Abstract] [Full Text]
|
|
|
|
|
|
T. Takeda, K. Ogino, E. Matsui, M. K. Cho, H. Kumagai, T. Miyake, K.-i. Arai, and H. Masai A Fission Yeast Gene, him1+/dfp1+, Encoding a Regulatory Subunit for Hsk1 Kinase, Plays Essential Roles in S-Phase Initiation as Well as in S-Phase Checkpoint Control and Recovery from DNA Damage Mol. Cell. Biol., August 1, 1999; 19(8): 5535 - 5547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. Brown and T. J. Kelly Cell cycle regulation of Dfp1, an activator of the Hsk1 protein kinase PNAS, July 20, 1999; 96(15): 8443 - 8448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Oshiro, J. C. Owens, Y. Shellman, R. A. Sclafani, and J. J. Li Cell Cycle Control of Cdc7p Kinase Activity through Regulation of Dbf4p Stability Mol. Cell. Biol., July 1, 1999; 19(7): 4888 - 4896. [Abstract] [Full Text] [PDF]
|
|
|
|
