Preventing re-replication of chromosomal DNA

To ensure its duplication, chromosomal DNA must be precisely duplicated in each cell cycle, with no sections left unreplicated, and no sections replicated more than once. Eukaryotic cells achieve this by dividing replication into two non-overlapping phases. During late mitosis and G1, replication origins are 'licensed' for replication by loading the minichromosome maintenance (Mcm) 2–7 proteins to form a pre-replicative complex. Mcm2–7 proteins are then essential for initiating and elongating replication forks during S phase. Recent data have provided biochemical and structural insight into the process of replication licensing and the mechanisms that regulate it during the cell cycle.

[1]  J. Moreau,et al.  XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis , 2000, Nature.

[2]  Z. Tu,et al.  Inhibiting the expression of DNA replication-initiation proteins induces apoptosis in human cancer cells. , 2003, Cancer research.

[3]  David M. Gilbert,et al.  In search of the holy replicator , 2004, Nature Reviews Molecular Cell Biology.

[4]  J. Blow,et al.  Reconstitution of licensed replication origins on Xenopus sperm nuclei using purified proteins , 2001, BMC Biochemistry.

[5]  R. Laskey,et al.  Human replication proteins hCdc21, hCdc46 and P1Mcm3 bind chromatin uniformly before S-phase and are displaced locally during DNA replication. , 1996, Journal of cell science.

[6]  T. Nishimoto,et al.  Proteolysis of DNA Replication Licensing Factor Cdt1 in S-phase Is Performed Independently of Geminin through Its N-terminal Region* , 2004, Journal of Biological Chemistry.

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

[8]  Filippo Del Bene,et al.  Direct interaction of geminin and Six3 in eye development , 2004, Nature.

[9]  Zoi Lygerou,et al.  The Human Licensing Factor for DNA Replication Cdt1 Accumulates in G1 and Is Destabilized after Initiation of S-phase* , 2001, The Journal of Biological Chemistry.

[10]  J. Blow,et al.  Cell Cycle Regulation of the Replication Licensing System: Involvement of a Cdk-dependent Inhibitor , 1997, The Journal of cell biology.

[11]  K. Stoeber,et al.  Molecular structure of human geminin , 2004, Nature Structural &Molecular Biology.

[12]  J. Nevins,et al.  E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. , 1998, Genes & development.

[13]  J. Bartek,et al.  Loss of Geminin induces rereplication in the presence of functional p53 , 2004, The Journal of cell biology.

[14]  K. Nasmyth,et al.  S-phase-promoting cyclin-dependent kinases prevent re-replication by inhibiting the transition of replication origins to a pre-replicative state , 1995, Current Biology.

[15]  J. Blow,et al.  Geminin Becomes Activated as an Inhibitor of Cdt1/RLF-B Following Nuclear Import , 2002, Current Biology.

[16]  P. Hamilton,et al.  Biochemical analysis. , 1966, Analytical chemistry.

[17]  J. Blow,et al.  Sequential MCM/P1 Subcomplex Assembly Is Required to Form a Heterohexamer with Replication Licensing Activity* , 2000, The Journal of Biological Chemistry.

[18]  B. Stillman,et al.  A double-hexamer archaeal minichromosome maintenance protein is an ATP-dependent DNA helicase. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[19]  K. Helin,et al.  Human Geminin promotes pre‐RC formation and DNA replication by stabilizing CDT1 in mitosis , 2004, The EMBO journal.

[20]  Z. Werb,et al.  Cyclins E1 and E2 are required for endoreplication in placental trophoblast giant cells , 2003, The EMBO journal.

[21]  T. McGarry,et al.  Geminin Has Dimerization, Cdt1-binding, and Destruction Domains That Are Required for Biological Activity* , 2004, Journal of Biological Chemistry.

[22]  P. O’Farrell,et al.  Fluctuations in Cyclin E levels are required for multiple rounds of endocycle S phase in Drosophila , 1998, Current Biology.

[23]  P. Nurse,et al.  Involvement of p34cdc2 in establishing the dependency of S phase on mitosis , 1991, Nature.

[24]  Z. Kelman,et al.  The single minichromosome maintenance protein of Methanobacterium thermoautotrophicum DeltaH contains DNA helicase activity. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[25]  D. Licatalosi,et al.  MCM Proteins Are Associated with RNA Polymerase II Holoenzyme , 1999, Molecular and Cellular Biology.

[26]  P. Kaldis,et al.  Cdk2 Knockout Mice Are Viable , 2003, Current Biology.

[27]  L. Drury,et al.  Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[28]  J. Newport,et al.  CpG Methylation of DNA Restricts Prereplication Complex Assembly in Xenopus Egg Extracts , 2003, Molecular and Cellular Biology.

[29]  Seiji Tanaka,et al.  Phosphorylation-dependent binding of mitotic cyclins to Cdc6 contributes to DNA replication control , 2004, Nature.

[30]  J. Leatherwood,et al.  Connecting ORC and Heterochromatin: Why? , 2003, Cell cycle.

[31]  L. Cooley,et al.  Control of DNA Replication and Chromosome Ploidy by Geminin and Cyclin A , 2002, Molecular and Cellular Biology.

[32]  Anindya Dutta,et al.  A p53-dependent checkpoint pathway prevents rereplication. , 2003, Molecular cell.

[33]  Joachim J Li,et al.  Loss of rereplication control in Saccharomyces cerevisiae results in extensive DNA damage. , 2004, Molecular biology of the cell.

[34]  J. Hamlin,et al.  Cdc6 Chromatin Affinity Is Unaffected by Serine-54 Phosphorylation, S-Phase Progression, and Overexpression of Cyclin A , 2004, Molecular and Cellular Biology.

[35]  J. Blow,et al.  Non-proteolytic inactivation of geminin requires CDK-dependent ubiquitination , 2004, Nature Cell Biology.

[36]  E. Kipreos,et al.  CUL-4 ubiquitin ligase maintains genome stability by restraining DNA-replication licensing , 2003, Nature.

[37]  J. Diffley,et al.  Uninterrupted MCM2-7 function required for DNA replication fork progression. , 2000, Science.

[38]  Xiaohua Wu,et al.  The SCFSkp2 Ubiquitin Ligase Complex Interacts with the Human Replication Licensing Factor Cdt1 and Regulates Cdt1 Degradation* , 2003, Journal of Biological Chemistry.

[39]  M. Lei,et al.  Physical interactions among Mcm proteins and effects of Mcm dosage on DNA replication in Saccharomyces cerevisiae , 1996, Molecular and cellular biology.

[40]  J. Kutok,et al.  Expression of geminin as a marker of cell proliferation in normal tissues and malignancies. , 2002, The American journal of pathology.

[41]  J. Blow,et al.  The role of Cdc6 in ensuring complete genome licensing and S phase checkpoint activation , 2004, The Journal of cell biology.

[42]  Xiaohua Wu,et al.  Cyclin-dependent Kinases Phosphorylate Human Cdt1 and Induce Its Degradation* , 2004, Journal of Biological Chemistry.

[43]  M. Kirschner,et al.  Geminin, an Inhibitor of DNA Replication, Is Degraded during Mitosis , 1998, Cell.

[44]  J. Newport,et al.  Identification of a Preinitiation Step in DNA Replication That Is Independent of Origin Recognition Complex and cdc6, but Dependent on cdk2 , 1998, The Journal of cell biology.

[45]  J. Parvin,et al.  Human CDC6/Cdc18 Associates with Orc1 and Cyclin-cdk and Is Selectively Eliminated from the Nucleus at the Onset of S Phase , 1998, Molecular and Cellular Biology.

[46]  B. Calvi,et al.  Drosophila double-parked is sufficient to induce re-replication during development and is regulated by cyclin E/CDK2 , 2004, Development.

[47]  S. Elsasser,et al.  Phosphorylation controls timing of Cdc6p destruction: A biochemical analysis. , 1999, Molecular biology of the cell.

[48]  Anindya Dutta,et al.  Rereplication by Depletion of Geminin Is Seen Regardless of p53 Status and Activates a G2/M Checkpoint , 2004, Molecular and Cellular Biology.

[49]  Seiji Tanaka,et al.  Interdependent nuclear accumulation of budding yeast Cdt1 and Mcm2–7 during G1 phase , 2002, Nature Cell Biology.

[50]  Carl Co,et al.  Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms , 2001, Nature.

[51]  P. Nurse,et al.  Maintenance of replication forks and the S-phase checkpoint by Cdc18p and Orp1p , 2002, Nature Cell Biology.

[52]  J. Blow,et al.  A role for the nuclear envelope in controlling DNA replication within the cell cycle , 1988, Nature.

[53]  Kiyoshi Ohtani,et al.  Regulation of cell growth-dependent expression of mammalian CDC6 gene by the cell cycle transcription factor E2F , 1998, Oncogene.

[54]  D. Gilbert,et al.  Mcm2, but Not Rpa, Is a Component of the Mammalian Early G1-Phase Prereplication Complex , 1999, The Journal of cell biology.

[55]  J. Gautier,et al.  DNA Unwinding Is an MCM Complex-dependent and ATP Hydrolysis-dependent Process* , 2004, Journal of Biological Chemistry.

[56]  B. Tye,et al.  Evidence for a Role of MCM (Mini-chromosome Maintenance)5 in Transcriptional Repression of Sub-telomeric and Ty-proximal Genes in Saccharomyces cerevisiae* , 2003, Journal of Biological Chemistry.

[57]  P. O’Farrell,et al.  Chromosome Association of Minichromosome Maintenance Proteins in Drosophila Endoreplication Cycles , 1998, The Journal of cell biology.

[58]  Domenico Maiorano,et al.  Specification of a DNA replication origin by a transcription complex , 2004, Nature Cell Biology.

[59]  J. Blow,et al.  Replication licensing — Origin licensing: defining the proliferative state? , 2002 .

[60]  C. Dumas,et al.  Crystal structure of the coiled-coil dimerization motif of geminin: structural and functional insights on DNA replication regulation. , 2004, Journal of molecular biology.

[61]  S. Harrison,et al.  Inhibition of Eukaryotic DNA Replication by Geminin Binding to Cdt1 , 2000 .

[62]  S. Bell,et al.  Interactions between two catalytically distinct MCM subgroups are essential for coordinated ATP hydrolysis and DNA replication. , 2001, Molecular cell.

[63]  T. McGarry,et al.  The Drosophila Geminin homolog: roles for Geminin in limiting DNA replication, in anaphase and in neurogenesis. , 2001, Genes & development.

[64]  M. van Heel,et al.  Hexameric ring structure of the full‐length archaeal MCM protein complex , 2003, EMBO reports.

[65]  M. Méchali,et al.  Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin , 2001, Nature Cell Biology.

[66]  Anindya Dutta,et al.  Architecture of the Human Origin Recognition Complex* , 2001, The Journal of Biological Chemistry.

[67]  S. Bell,et al.  ATP hydrolysis by ORC catalyzes reiterative Mcm2-7 assembly at a defined origin of replication. , 2004, Molecular cell.

[68]  L. Drury,et al.  The cyclin-dependent kinase Cdc28p regulates distinct modes of Cdc6p proteolysis during the budding yeast cell cycle , 2000, Current Biology.

[69]  Bruce Stillman,et al.  Chromatin Association of Human Origin Recognition Complex, Cdc6, and Minichromosome Maintenance Proteins during the Cell Cycle: Assembly of Prereplication Complexes in Late Mitosis , 2000, Molecular and Cellular Biology.

[70]  J. Walter,et al.  Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts. , 2005, Genes & development.

[71]  M. DePamphilis,et al.  Role for Cdk1 (Cdc2)/Cyclin A in Preventing the Mammalian Origin Recognition Complex's Largest Subunit (Orc1) from Binding to Chromatin during Mitosis , 2004, Molecular and Cellular Biology.

[72]  M. Seki,et al.  Licensing for DNA replication requires a strict sequential assembly of Cdc6 and Cdt1 onto chromatin in Xenopus egg extracts , 2005, Nucleic acids research.

[73]  Yunje Cho,et al.  Structural basis for inhibition of the replication licensing factor Cdt1 by geminin , 2004, Nature.

[74]  Y. Ishimi.  A DNA Helicase Activity Is Associated with an MCM4, -6, and -7 Protein Complex* , 1997, The Journal of Biological Chemistry.

[75]  P. Nurse,et al.  Cdt1 and geminin are down-regulated upon cell cycle exit and are over-expressed in cancer-derived cell lines. , 2004, European journal of biochemistry.

[76]  F. Cross,et al.  Interaction of the S-phase cyclin Clb5 with an "RXL" docking sequence in the initiator protein Orc6 provides an origin-localized replication control switch. , 2004, Genes & development.

[77]  Bruce Stillman,et al.  Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins. , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[78]  Y. Tatsumi,et al.  Cdt1 Phosphorylation by Cyclin A-dependent Kinases Negatively Regulates Its Function without Affecting Geminin Binding* , 2004, Journal of Biological Chemistry.

[79]  J. Leatherwood,et al.  Control of DNA Rereplication via Cdc2 Phosphorylation Sites in the Origin Recognition Complex , 2001, Molecular and Cellular Biology.

[80]  Kiyoshi Ohtani,et al.  Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F , 1999, Oncogene.

[81]  R. Laskey,et al.  Human Minichromosome Maintenance Proteins and Human Origin Recognition Complex 2 Protein on Chromatin* , 1998, The Journal of Biological Chemistry.

[82]  D. Takeda,et al.  A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition. , 2004, Molecular cell.

[83]  D. Lane,et al.  Cell type-specific responses of human cells to inhibition of replication licensing , 2002, Oncogene.

[84]  Zoi Lygerou,et al.  The Cdt1 protein is required to license DNA for replication in fission yeast , 2000, Nature.

[85]  Kazumasa Yoshida,et al.  Intrinsic nuclear import activity of geminin is essential to prevent re‐initiation of DNA replication in Xenopus eggs , 2004, Genes to cells : devoted to molecular & cellular mechanisms.

[86]  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.

[87]  M. Pacek,et al.  A requirement for MCM7 and Cdc45 in chromosome unwinding during eukaryotic DNA replication , 2004, The EMBO journal.

[88]  J. Decaprio,et al.  Structure of the replicative helicase of the oncoprotein SV40 large tumour antigen , 2003, Nature.

[89]  J. Blow,et al.  Cdt1 downregulation by proteolysis and geminin inhibition prevents DNA re‐replication in Xenopus , 2005, The EMBO journal.

[90]  P. O’Farrell,et al.  Chromosome Association of Minichromosome Maintenance Proteins in Drosophila Mitotic Cycles , 1997, The Journal of cell biology.

[91]  P. Jallepalli,et al.  Regulation of the replication initiator protein p65cdc18 by CDK phosphorylation. , 1997, Genes & development.

[92]  J. Diffley,et al.  Once and only once upon a time: specifying and regulating origins of DNA replication in eukaryotic cells. , 1996, Genes & development.

[93]  P. Nurse,et al.  Stable Association of Mitotic Cyclin B/Cdc2 to Replication Origins Prevents Endoreduplication , 2002, Cell.

[94]  Robert T. Johnson,et al.  Mammalian Cell Fusion : Studies on the Regulation of DNA Synthesis and Mitosis , 1970, Nature.

[95]  G. Williams,et al.  Improved cervical smear assessment using antibodies against proteins that regulate DNA replication. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[96]  B. Stillman,et al.  Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication. , 2002, Molecular cell.

[97]  Y. Minami,et al.  Rapid Degradation of Cdt1 upon UV-induced DNA Damage Is Mediated by SCFSkp2 Complex* , 2004, Journal of Biological Chemistry.

[98]  Pierre Dubus,et al.  Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice , 2003, Nature Genetics.

[99]  M. DePamphilis,et al.  Mammalian Orc1 Protein Is Selectively Released from Chromatin and Ubiquitinated during the S-to-M Transition in the Cell Division Cycle , 2002, Molecular and Cellular Biology.

[100]  S. Vashee,et al.  Assembly of the Human Origin Recognition Complex* , 2001, The Journal of Biological Chemistry.

[101]  J. Blow,et al.  Changes in association of the Xenopus origin recognition complex with chromatin on licensing of replication origins. , 1999, Journal of cell science.

[102]  T. Mizuno,et al.  Mouse Geminin Inhibits Not Only Cdt1-MCM6 Interactions but Also a Novel Intrinsic Cdt1 DNA Binding Activity* , 2002, The Journal of Biological Chemistry.

[103]  J. Gautier,et al.  The Intrinsic DNA Helicase Activity of Methanobacterium thermoautotrophicum ΔH Minichromosome Maintenance Protein* , 2000, The Journal of Biological Chemistry.

[104]  Jianyu Zheng,et al.  Radiation-mediated proteolysis of CDT1 by CUL4–ROC1 and CSN complexes constitutes a new checkpoint , 2003, Nature Cell Biology.

[105]  Craig M. Ogata,et al.  The structure and function of MCM from archaeal M. Thermoautotrophicum , 2003, Nature Structural Biology.

[106]  R. Laskey,et al.  Chromatin-bound Cdc6 persists in S and G2 phases in human cells, while soluble Cdc6 is destroyed in a cyclin A-cdk2 dependent process. , 2000, Journal of cell science.

[107]  M. Méchali,et al.  Recombinant Cdt1 Induces Rereplication of G2 Nuclei in Xenopus Egg Extracts , 2005, Current Biology.

[108]  H. Nishitani,et al.  DNA replication licensing. , 2004, Frontiers in bioscience : a journal and virtual library.

[109]  R. Laskey,et al.  Distinct roles for cyclins E and A during DNA replication complex assembly and activation , 2002, Nature Cell Biology.

[110]  Jiri Bartek,et al.  Phosphorylation of mammalian CDC6 by Cyclin A/CDK2 regulates its subcellular localization , 1999, The EMBO journal.

[111]  R. Laskey,et al.  The nuclear envelope prevents reinitiation of replication by regulating the binding of MCM3 to chromatin in Xenopus egg extracts , 1995, Current Biology.

[112]  J. Nevins,et al.  The Regulated Association of Cdt1 with Minichromosome Maintenance Proteins and Cdc6 in Mammalian Cells* , 2004, Journal of Biological Chemistry.

[113]  Stephen E. Kearsey,et al.  G1-phase and B-type cyclins exclude the DNA-replication factor Mcm4 from the nucleus , 1999, Nature Cell Biology.

[114]  J. Blow,et al.  Replication licensing--defining the proliferative state? , 2002, Trends in cell biology.

[115]  Yan Geng,et al.  Cyclin E Ablation in the Mouse , 2003, Cell.

[116]  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.

[117]  S. Elledge,et al.  Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[118]  R. Knippers,et al.  Interactions of human nuclear proteins P1Mcm3 and P1Cdc46. , 1995, European journal of biochemistry.

[119]  Kaoru Irie,et al.  Clb/Cdc28 kinases promote nuclear export of the replication initiator proteins Mcm2–7 , 2000, Current Biology.

[120]  J. Pines,et al.  Human replication protein Cdc6 prevents mitosis through a checkpoint mechanism that implicates Chk1 , 2003, The EMBO journal.

[121]  J. Schweizer,et al.  Simian virus 40 T-antigen DNA helicase is a hexamer which forms a binary complex during bidirectional unwinding from the viral origin of DNA replication , 1992, Journal of virology.

[122]  R. Laskey,et al.  A rotary pumping model for helicase function of MCM proteins at a distance from replication forks , 2003, EMBO reports.

[123]  M. Kessel,et al.  The cell-cycle regulator geminin inhibits Hox function through direct and polycomb-mediated interactions , 2004, Nature.

[124]  G. Williams,et al.  DNA replication licensing and human cell proliferation. , 2001, Journal of cell science.

[125]  T. Prokhorova,et al.  MCM2–7 Complexes Bind Chromatin in a Distributed Pattern Surrounding the Origin Recognition Complex inXenopus Egg Extracts* , 2002, The Journal of Biological Chemistry.