CDC45

Summary

Gene Symbol: CDC45
Description: DNA replication initiation factor CDC45
Alias: SLD4, DNA replication initiation factor CDC45
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Morohashi H, Maculins T, Labib K. The amino-terminal TPR domain of Dia2 tethers SCF(Dia2) to the replisome progression complex. Curr Biol. 2009;19:1943-9 pubmed publisher
    ..Our findings suggest that the amino-terminal domains of other F box proteins might also play an analogous regulatory role, controlling the localization of the cognate SCF complexes. ..
  2. Tanaka S, Umemori T, Hirai K, Muramatsu S, Kamimura Y, Araki H. CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast. Nature. 2007;445:328-32 pubmed
    ..Here we show that both an allele of CDC45 (JET1) and high-copy DPB11, in combination with Sld2-11D, separately confer CDK-independent DNA replication...
  3. Kamimura Y, Tak Y, Sugino A, Araki H. Sld3, which interacts with Cdc45 (Sld4), functions for chromosomal DNA replication in Saccharomyces cerevisiae. EMBO J. 2001;20:2097-107 pubmed
    b>Cdc45, which binds to the minichromosomal maintenance (Mcm) proteins, has a pivotal role in the initiation and elongation steps of chromosomal DNA replication in eukaryotes...
  4. De Piccoli G, Katou Y, Itoh T, Nakato R, Shirahige K, Labib K. Replisome stability at defective DNA replication forks is independent of S phase checkpoint kinases. Mol Cell. 2012;45:696-704 pubmed publisher
  5. Kilkenny M, De Piccoli G, Perera R, Labib K, Pellegrini L. A conserved motif in the C-terminal tail of DNA polymerase α tethers primase to the eukaryotic replisome. J Biol Chem. 2012;287:23740-7 pubmed publisher
    ..These findings indicate that tethering of primase to the replisome by pol α is critical for the normal action of DNA replication forks in eukaryotic cells. ..
  6. Sengupta S, van Deursen F, De Piccoli G, Labib K. Dpb2 integrates the leading-strand DNA polymerase into the eukaryotic replisome. Curr Biol. 2013;23:543-52 pubmed publisher
    ..A central unresolved issue is how the Cdc45-MCM-GINS helicase is linked to DNA polymerase epsilon, which synthesizes the leading strand at replication forks ..
  7. Sheu Y, Stillman B. Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression. Mol Cell. 2006;24:101-13 pubmed
    ..Prior to initiation of DNA synthesis from each origin, a preinitiation complex (pre-IC) containing Cdc45 and other proteins is formed...
  8. Katou Y, Kanoh Y, Bando M, Noguchi H, Tanaka H, Ashikari T, et al. S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex. Nature. 2003;424:1078-83 pubmed
    ..When hydroxyurea blocks chromosomal replication, this assembly forms a stable pausing structure that serves to anchor subsequent DNA repair events. ..
  9. Tanaka H, Katou Y, Yagura M, Saitoh K, Itoh T, Araki H, et al. Ctf4 coordinates the progression of helicase and DNA polymerase alpha. Genes Cells. 2009;14:807-20 pubmed publisher
    ..These results lead us to propose that Ctf4 is a key connector between DNA helicase and Pol alpha and is required for the coordinated progression of the replisome. ..

More Information

Publications71

  1. Tanaka S, Diffley J. Interdependent nuclear accumulation of budding yeast Cdt1 and Mcm2-7 during G1 phase. Nat Cell Biol. 2002;4:198-207 pubmed
    ..Cdt1p interacts with the Mcm2--7p complex, and the nuclear accumulation of these proteins during G1 is interdependent. This coregulation of Cdt1p and Mcm2-7p represents a novel level of pre-RC control. ..
  2. Calzada A, Hodgson B, Kanemaki M, Bueno A, Labib K. Molecular anatomy and regulation of a stable replisome at a paused eukaryotic DNA replication fork. Genes Dev. 2005;19:1905-19 pubmed
    ..The budding yeast proteins Mrc1 and Tof1 associate with the putative MCM-Cdc45 helicase and limit progression of the replisome when nucleotides are depleted, and the checkpoint kinases Mec1 and ..
  3. Tanaka T, Umemori T, Endo S, Muramatsu S, Kanemaki M, Kamimura Y, et al. Sld7, an Sld3-associated protein required for efficient chromosomal DNA replication in budding yeast. EMBO J. 2011;30:2019-30 pubmed publisher
    ..the cell cycle, Sld7 forms a complex with Sld3, which associates with replication origins in a complex with Cdc45, binds to Dpb11 when phosphorylated by cyclin-dependent kinase, and dissociates from origins once DNA replication ..
  4. Kamimura Y, Masumoto H, Sugino A, Araki H. Sld2, which interacts with Dpb11 in Saccharomyces cerevisiae, is required for chromosomal DNA replication. Mol Cell Biol. 1998;18:6102-9 pubmed
    ..These results strongly suggest the involvement of the Dpb11-Sld2 complex in a step close to the initiation of DNA replication. ..
  5. Mattarocci S, Shyian M, Lemmens L, Damay P, Altintas D, Shi T, et al. Rif1 controls DNA replication timing in yeast through the PP1 phosphatase Glc7. Cell Rep. 2014;7:62-9 pubmed publisher
    ..Our data thus link Rif1 to negative regulation of replication origin firing through recruitment of the Glc7 phosphatase. ..
  6. Pérez Arnaiz P, Bruck I, Colbert M, Kaplan D. An intact Mcm10 coiled-coil interaction surface is important for origin melting, helicase assembly and the recruitment of Pol-? to Mcm2-7. Nucleic Acids Res. 2017;45:7261-7275 pubmed publisher
    Mcm10 is an essential eukaryotic factor required for DNA replication. The replication fork helicase is composed of Cdc45, Mcm2-7 and GINS (CMG)...
  7. Su N, Flick K, Kaiser P. The F-box protein Met30 is required for multiple steps in the budding yeast cell cycle. Mol Cell Biol. 2005;25:3875-85 pubmed
    ..immunoprecipitation experiments revealed significantly lower levels of the replication factors Mcm4, Mcm7, and Cdc45 at replication origins in met30 mutants than in wild-type cells...
  8. Bruck I, Dhingra N, Martinez M, Kaplan D. Dpb11 may function with RPA and DNA to initiate DNA replication. PLoS ONE. 2017;12:e0177147 pubmed publisher
    ..Expression of dpb11-m1,2,3,5,?C also results in diminished GINS interaction with Mcm2-7 during S phase, while Cdc45 interaction with Mcm2-7 is like wild-type...
  9. van Deursen F, Sengupta S, De Piccoli G, Sanchez Diaz A, Labib K. Mcm10 associates with the loaded DNA helicase at replication origins and defines a novel step in its activation. EMBO J. 2012;31:2195-206 pubmed publisher
    ..Strikingly, the other essential helicase subunits Cdc45 and GINS were still recruited to Mcm2-7 when cells entered S-phase without Mcm10, but origin unwinding was blocked...
  10. Bruck I, Kaplan D. Origin single-stranded DNA releases Sld3 protein from the Mcm2-7 complex, allowing the GINS tetramer to bind the Mcm2-7 complex. J Biol Chem. 2011;286:18602-13 pubmed publisher
    The replication fork helicase in eukaryotic cells is comprised of Cdc45, Mcm2-7, and GINS (CMG complex)...
  11. Quan Y, Xia Y, Liu L, Cui J, Li Z, Cao Q, et al. Cell-Cycle-Regulated Interaction between Mcm10 and Double Hexameric Mcm2-7 Is Required for Helicase Splitting and Activation during S Phase. Cell Rep. 2015;13:2576-2586 pubmed publisher
    ..Therefore, we propose an essential role for Mcm10 in Mcm2-7 remodeling through formation of a cell-cycle-regulated supercomplex with DHs. ..
  12. Irlbacher H, Franke J, Manke T, Vingron M, Ehrenhofer Murray A. Control of replication initiation and heterochromatin formation in Saccharomyces cerevisiae by a regulator of meiotic gene expression. Genes Dev. 2005;19:1811-22 pubmed
    ..Full initiation activity of these origins required Sum1, and their origin activity was decreased upon removal of the Sum1-binding site. Thus, Sum1 constitutes a novel global regulator of replication initiation in yeast. ..
  13. Naylor M, Li J, Osborn A, Elledge S. Mrc1 phosphorylation in response to DNA replication stress is required for Mec1 accumulation at the stalled fork. Proc Natl Acad Sci U S A. 2009;106:12765-70 pubmed publisher
    ..Together these results reveal new insight into how Mrc1 facilitates checkpoint signal amplification at stalled replication forks. ..
  14. Mantiero D, Mackenzie A, Donaldson A, Zegerman P. Limiting replication initiation factors execute the temporal programme of origin firing in budding yeast. EMBO J. 2011;30:4805-14 pubmed publisher
  15. Dalton S, Hopwood B. Characterization of Cdc47p-minichromosome maintenance complexes in Saccharomyces cerevisiae: identification of Cdc45p as a subunit. Mol Cell Biol. 1997;17:5867-75 pubmed
    ..This argues that assembly of Cdc47p into complexes with other MCM polypeptides is important for its role in the initiation of chromosomal DNA replication. ..
  16. Kubota T, Hiraga S, Yamada K, Lamond A, Donaldson A. Quantitative proteomic analysis of chromatin reveals that Ctf18 acts in the DNA replication checkpoint. Mol Cell Proteomics. 2011;10:M110.005561 pubmed publisher
    ..ctf18Δ cells exhibited increased chromatin association of replisome progression complex components including Cdc45, Ctf4, and GINS complex subunits, the polymerase processivity clamp PCNA and the single-stranded DNA-binding ..
  17. Hahn S, Maurer P, Caesar S, Schlenstedt G. Classical NLS proteins from Saccharomyces cerevisiae. J Mol Biol. 2008;379:678-94 pubmed publisher
    ..We show for the first time that endogenous S. cerevisiae proteins Prp20, Cdc6, Swi5, Cdc45, and Clb2 fulfill all of these criteria identifying them as authentic yeast cNLS cargos...
  18. Sclafani R, Tecklenburg M, Pierce A. The mcm5-bob1 bypass of Cdc7p/Dbf4p in DNA replication depends on both Cdk1-independent and Cdk1-dependent steps in Saccharomyces cerevisiae. Genetics. 2002;161:47-57 pubmed
    ..Thus Cdc7p and Cdk1p kinases catalyze the initiation of DNA replication at several distinct steps, of which only a subset is bypassed by the mcm5-bob1 mutation. ..
  19. Zou L, Stillman B. Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading of Cdc45p onto chromatin. Science. 1998;280:593-6 pubmed
  20. Sawyer S, Cheng I, Chai W, Tye B. Mcm10 and Cdc45 cooperate in origin activation in Saccharomyces cerevisiae. J Mol Biol. 2004;340:195-202 pubmed
    ..Association of Cdc45 with ARS1 is reduced in the mcm10-1 mutant, suggesting that Mcm10 is involved in recruiting Cdc45 to the pre-RC...
  21. Lydeard J, Lipkin Moore Z, Sheu Y, Stillman B, Burgers P, Haber J. Break-induced replication requires all essential DNA replication factors except those specific for pre-RC assembly. Genes Dev. 2010;24:1133-44 pubmed publisher
    ..Here we show that BIR requires the replicative DNA helicase (Cdc45, the GINS, and Mcm2-7 proteins) as well as Cdt1...
  22. Bruck I, Kaplan D. Conserved mechanism for coordinating replication fork helicase assembly with phosphorylation of the helicase. Proc Natl Acad Sci U S A. 2015;112:11223-8 pubmed publisher
    ..minichromosome maintenance 2 (Mcm2) during S phase in yeast, and Sld3 recruits cell division cycle 45 (Cdc45) to minichromosome maintenance 2-7 (Mcm2-7)...
  23. Fiorani P, Reid R, Schepis A, Jacquiau H, Guo H, Thimmaiah P, et al. The deubiquitinating enzyme Doa4p protects cells from DNA topoisomerase I poisons. J Biol Chem. 2004;279:21271-81 pubmed
    ..Additional studies suggest a role for Doa4p in the Rad9p checkpoint response to Top1p poisons. These findings indicate a functional link between ubiquitin-mediated proteolysis and cellular resistance to CPT-induced DNA damage. ..
  24. Tsai F, Vijayraghavan S, Prinz J, MacAlpine H, MacAlpine D, Schwacha A. Mcm2-7 Is an Active Player in the DNA Replication Checkpoint Signaling Cascade via Proposed Modulation of Its DNA Gate. Mol Cell Biol. 2015;35:2131-43 pubmed publisher
    ..We infer that this conformational change is required for its DRC role and propose that it allosterically facilitates Rad53 activation to ensure a replication-specific checkpoint response. ..
  25. Rehman M, Fourel G, Mathews A, Ramdin D, Espinosa M, Gilson E, et al. Differential requirement of DNA replication factors for subtelomeric ARS consensus sequence protosilencers in Saccharomyces cerevisiae. Genetics. 2006;174:1801-10 pubmed
    ..Here we analyze the effect of mutations in DNA replication factors (mcm5-461, mcm5-1, orc2-1, orc5-1, cdc45-1, cdc6-1, and cdc7-1) on the silencing of a group of reporter constructs, which contain different combinations of ..
  26. Bruck I, Kaplan D. GINS and Sld3 compete with one another for Mcm2-7 and Cdc45 binding. J Biol Chem. 2011;286:14157-67 pubmed publisher
    ..GINS binds to Cdc45 and Mcm2-7 to form the replication fork helicase in eukaryotes...
  27. Herrera M, Tognetti S, Riera A, Zech J, Clarke P, Fernández Cid A, et al. A reconstituted system reveals how activating and inhibitory interactions control DDK dependent assembly of the eukaryotic replicative helicase. Nucleic Acids Res. 2015;43:10238-50 pubmed publisher
    ..CDK) direct with the help of a large number of helicase-activation factors the assembly of a Cdc45-MCM2-7-GINS (CMG) complex...
  28. Homesley L, Lei M, Kawasaki Y, Sawyer S, Christensen T, Tye B. Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins. Genes Dev. 2000;14:913-26 pubmed
    ..These results suggest that Mcm10, like Mcm7, is a critical component of the prereplication chromatin and that interaction between Mcm10 and Mcm7 is required for proper replication initiation and prompt release of origin-bound factors. ..
  29. Nedelcheva M, Roguev A, Dolapchiev L, Shevchenko A, Taskov H, Shevchenko A, et al. Uncoupling of unwinding from DNA synthesis implies regulation of MCM helicase by Tof1/Mrc1/Csm3 checkpoint complex. J Mol Biol. 2005;347:509-21 pubmed
    ..In concordance with this suggestion, we found that the Tof1/Csm3/Mrc1 checkpoint complex interacts directly with the MCM helicase during both replication fork progression and when the replication fork is stalled. ..
  30. Maric M, Maculins T, De Piccoli G, Labib K. Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication. Science. 2014;346:1253596 pubmed publisher
    ..universal mechanism in eukaryotic cells, involving the assembly and activation at replication origins of the CMG (Cdc45-MCM-GINS) DNA helicase, which is essential for the progression of replication forks...
  31. Simon A, Zhou J, Perera R, van Deursen F, Evrin C, Ivanova M, et al. A Ctf4 trimer couples the CMG helicase to DNA polymerase α in the eukaryotic replisome. Nature. 2014;510:293-297 pubmed publisher
    ..Here we define the molecular mechanism by which the yeast Ctf4 protein links the Cdc45-MCM-GINS (CMG) DNA helicase to DNA polymerase α (Pol α) within the replisome...
  32. Bando M, Katou Y, Komata M, Tanaka H, Itoh T, Sutani T, et al. Csm3, Tof1, and Mrc1 form a heterotrimeric mediator complex that associates with DNA replication forks. J Biol Chem. 2009;284:34355-65 pubmed publisher
    ..In agreement with previous observations in yeast cells, the results of a baculovirus coexpression system showed that these three proteins interact directly with each other to form a mediator complex in the absence of replication forks. ..
  33. Maculins T, Nkosi P, Nishikawa H, Labib K. Tethering of SCF(Dia2) to the Replisome Promotes Efficient Ubiquitylation and Disassembly of the CMG Helicase. Curr Biol. 2015;25:2254-9 pubmed publisher
    Disassembly of the Cdc45-MCM-GINS (CMG) DNA helicase, which unwinds the parental DNA duplex at eukaryotic replication forks, is the key regulated step during replication termination but is poorly understood...
  34. Pérez Arnaiz P, Kaplan D. An Mcm10 Mutant Defective in ssDNA Binding Shows Defects in DNA Replication Initiation. J Mol Biol. 2016;428:4608-4625 pubmed publisher
    ..These data suggest that DNA binding by Mcm10 is essential for the initiation of DNA replication. ..
  35. Villa F, Simon A, Ortiz Bazan M, Kilkenny M, Wirthensohn D, Wightman M, et al. Ctf4 Is a Hub in the Eukaryotic Replisome that Links Multiple CIP-Box Proteins to the CMG Helicase. Mol Cell. 2016;63:385-96 pubmed publisher
    ..Most strikingly, Ctf4-dependent recruitment of CIP-box proteins couples other processes to DNA synthesis, including rDNA copy-number regulation. ..
  36. Tanaka S, Araki H. Multiple regulatory mechanisms to inhibit untimely initiation of DNA replication are important for stable genome maintenance. PLoS Genet. 2011;7:e1002136 pubmed publisher
    ..These findings highlight the importance of having multiple inhibitory mechanisms to prevent the untimely initiation of chromosome replication to preserve stable genome maintenance over generations in eukaryotes. ..
  37. Hennessy K, Lee A, Chen E, Botstein D. A group of interacting yeast DNA replication genes. Genes Dev. 1991;5:958-69 pubmed
    ..genes CDC46 and CDC47 were originally isolated as suppressors of mutations in two other cell-division-cycle genes (CDC45 and CDC54)...
  38. Aparicio O, Weinstein D, Bell S. Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase. Cell. 1997;91:59-69 pubmed
    ..Our results identify protein components of the pre-RC and a novel replication complex appearing at the G1/S transition (the RC), and suggest that after initiation MCM proteins and Cdc45p move with eukaryotic replication forks. ..
  39. Reid R, Fiorani P, Sugawara M, Bjornsti M. CDC45 and DPB11 are required for processive DNA replication and resistance to DNA topoisomerase I-mediated DNA damage. Proc Natl Acad Sci U S A. 1999;96:11440-5 pubmed
    ..Two mutants isolated, cdc45-10 and dpb11-10, exhibited specific defects in DNA replication and a synthetic lethal phenotype in the absence of ..
  40. Dhingra N, Bruck I, Smith S, Ning B, Kaplan D. Dpb11 protein helps control assembly of the Cdc45·Mcm2-7·GINS replication fork helicase. J Biol Chem. 2015;290:7586-601 pubmed publisher
    ..The replication fork helicase in eukaryotes is composed of Cdc45, Mcm2-7, and GINS...
  41. Bruck I, Kaplan D. Cdc45 protein-single-stranded DNA interaction is important for stalling the helicase during replication stress. J Biol Chem. 2013;288:7550-63 pubmed publisher
    ..b>Cdc45 activates the Mcm2-7 helicase...
  42. García Rodríguez L, De Piccoli G, Marchesi V, Jones R, Edmondson R, Labib K. A conserved Polϵ binding module in Ctf18-RFC is required for S-phase checkpoint activation downstream of Mec1. Nucleic Acids Res. 2015;43:8830-8 pubmed publisher
    ..These findings indicate that the association of Ctf18-RFC with Pol ϵ at defective replication forks is a key step in activation of the S-phase checkpoint. ..
  43. Yaakov G, Duch A, Garcia Rubio M, Clotet J, Jimenez J, Aguilera A, et al. The stress-activated protein kinase Hog1 mediates S phase delay in response to osmostress. Mol Biol Cell. 2009;20:3572-82 pubmed publisher
    ..The two mechanisms of Hog1 action lead to delayed firing of origins and prolonged replication, respectively. The Hog1-dependent delay of replication could be important to allow Hog1 to induce gene expression before replication. ..
  44. Araki Y, Kawasaki Y, Sasanuma H, Tye B, Sugino A. Budding yeast mcm10/dna43 mutant requires a novel repair pathway for viability. Genes Cells. 2003;8:465-80 pubmed
    ..components of the pre-RC and pre-IC and are represented by SLM3, 4 and 5 which are allelic to MCM7, MCM2 and CDC45, respectively...
  45. Zou L, Stillman B. 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. 2000;20:3086-96 pubmed
    ..These results suggest that the complex containing Cdc45p, RPA, and MCMs is involved in origin unwinding and assembly of replication forks at each origin. ..
  46. Tanaka S, Nakato R, Katou Y, Shirahige K, Araki H. Origin association of Sld3, Sld7, and Cdc45 proteins is a key step for determination of origin-firing timing. Curr Biol. 2011;21:2055-63 pubmed publisher
    ..We show that origin association of the low-abundance replication proteins Sld3, Sld7, and Cdc45 is the key to determining the temporal order of origin firing...
  47. Zou L, Mitchell J, Stillman B. CDC45, a novel yeast gene that functions with the origin recognition complex and Mcm proteins in initiation of DNA replication. Mol Cell Biol. 1997;17:553-63 pubmed
    The CDC45 gene of Saccharomyces cerevisiae was isolated by complementation of the cold-sensitive cdc45-1 mutant and shown to be essential for cell viability...
  48. Watase G, Takisawa H, Kanemaki M. Mcm10 plays a role in functioning of the eukaryotic replicative DNA helicase, Cdc45-Mcm-GINS. Curr Biol. 2012;22:343-9 pubmed publisher
    ..A key process of replication initiation is to convert inactive Mcm2-7 to active Cdc45-Mcm-GINS (CMG) replicative helicase [2]...
  49. Bastia D, Srivastava P, Zaman S, Choudhury M, Mohanty B, Bacal J, et al. Phosphorylation of CMG helicase and Tof1 is required for programmed fork arrest. Proc Natl Acad Sci U S A. 2016;113:E3639-48 pubmed publisher
    ..chromosome maintenance (Mcm) 2-7 complex, which is known to require phosphorylation by DDK to form an active CMG [Cdc45 (cell division cycle gene 45), Mcm2-7, GINS (Go, Ichi, Ni, and San)] helicase...
  50. Ricke R, Bielinsky A. Mcm10 regulates the stability and chromatin association of DNA polymerase-alpha. Mol Cell. 2004;16:173-85 pubmed
    ..phase results in degradation of the catalytic subunit of polalpha, without affecting other fork components such as Cdc45. We propose that Mcm10 stabilizes polalpha and recruits the complex to replication origins...
  51. Aucher W, Becker E, Ma E, Miron S, Martel A, Ochsenbein F, et al. A strategy for interaction site prediction between phospho-binding modules and their partners identified from proteomic data. Mol Cell Proteomics. 2010;9:2745-59 pubmed publisher
    ..In this screen we detected 11 partners, including Cdc7 and Cdc45, essential components of the DNA replication machinery...
  52. Hardy C. Identification of Cdc45p, an essential factor required for DNA replication. Gene. 1997;187:239-46 pubmed
    b>CDC45 is an essential gene required for initiation of DNA replication in the budding yeast Saccharomyces cerevisiae...
  53. Langston L, Mayle R, Schauer G, Yurieva O, Zhang D, Yao N, et al. Mcm10 promotes rapid isomerization of CMG-DNA for replisome bypass of lagging strand DNA blocks. elife. 2017;6: pubmed publisher
    ..We demonstrate that bypass occurs without displacement of the blocks and therefore Mcm10 must isomerize the CMG-DNA complex to achieve the bypass function. ..
  54. Zegerman P, Diffley J. Checkpoint-dependent inhibition of DNA replication initiation by Sld3 and Dbf4 phosphorylation. Nature. 2010;467:474-8 pubmed publisher
    ..Our results explain how checkpoints regulate origin firing and demonstrate that the slowing of S phase by the 'intra-S checkpoint' is primarily due to the inhibition of origin firing. ..
  55. Langston L, Zhang D, Yurieva O, Georgescu R, Finkelstein J, Yao N, et al. CMG helicase and DNA polymerase ε form a functional 15-subunit holoenzyme for eukaryotic leading-strand DNA replication. Proc Natl Acad Sci U S A. 2014;111:15390-5 pubmed publisher
    ..The CMG (Cdc45-MCM-GINS) helicase surrounds the leading strand and is proposed to recruit Pol ε for leading-strand synthesis, ..
  56. Itou H, Muramatsu S, Shirakihara Y, Araki H. Crystal structure of the homology domain of the eukaryotic DNA replication proteins Sld3/Treslin. Structure. 2014;22:1341-1347 pubmed publisher
    ..The domain consists of two segments with 12 helices and is sufficient to bind to Cdc45, the essential helicase component...
  57. Yoshida K, Bacal J, Desmarais D, Padioleau I, Tsaponina O, Chabes A, et al. The histone deacetylases sir2 and rpd3 act on ribosomal DNA to control the replication program in budding yeast. Mol Cell. 2014;54:691-7 pubmed publisher
    ..Together, these data indicate that HDACs control the replication timing program in budding yeast by modulating the ability of repeated origins to compete with single-copy origins for limiting initiation factors. ..
  58. Froelich C, Kang S, Epling L, Bell S, Enemark E. A conserved MCM single-stranded DNA binding element is essential for replication initiation. elife. 2014;3:e01993 pubmed publisher
    ..Our findings identify an important MCM-ssDNA interaction and suggest it functions during helicase activation to select the strand for translocation. DOI: http://dx.doi.org/10.7554/eLife.01993.001...
  59. Dhillon N, Oki M, Szyjka S, Aparicio O, Kamakaka R. H2A.Z functions to regulate progression through the cell cycle. Mol Cell Biol. 2006;26:489-501 pubmed
    ..We also found that H2A.Z localized to the promoters of cyclin genes, and cells lacking H2A.Z were delayed in the induction of these cyclin genes. Several different models are proposed to explain these observations. ..
  60. Sun J, Shi Y, Georgescu R, Yuan Z, Chait B, Li H, et al. The architecture of a eukaryotic replisome. Nat Struct Mol Biol. 2015;22:976-82 pubmed publisher
    At the eukaryotic DNA replication fork, it is widely believed that the Cdc45-Mcm2-7-GINS (CMG) helicase is positioned in front to unwind DNA and that DNA polymerases trail behind the helicase...
  61. Miyazawa Onami M, Araki H, Tanaka S. Pre-initiation complex assembly functions as a molecular switch that splits the Mcm2-7 double hexamer. EMBO Rep. 2017;18:1752-1761 pubmed publisher
    ..In the pre-IC, the Mcm2-7 double hexamer is separated into single hexamers, as in the active helicase. Our data indicate that pre-IC assembly functions as an all-or-nothing molecular switch that splits the Mcm2-7 double hexamer. ..
  62. Hopwood B, Dalton S. Cdc45p assembles into a complex with Cdc46p/Mcm5p, is required for minichromosome maintenance, and is essential for chromosomal DNA replication. Proc Natl Acad Sci U S A. 1996;93:12309-14 pubmed
    We report the isolation and characterization of CDC45, which encodes a polypeptide of 650 amino acids that is essential for the initiation of chromosomal DNA replication in the budding yeast, Saccharomyces cerevisiae...