Affinage

CDC45

Cell division control protein 45 homolog · UniProt O75419

Length
566 aa
Mass
65.6 kDa
Annotated
2026-04-28
100 papers in source corpus 66 papers cited in narrative 66 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDC45 is an essential subunit of the CMG (Cdc45–MCM2–7–GINS) replicative helicase that activates DNA unwinding at replication origins and travels with the replisome during elongation. Cdc45 is recruited to licensed origins through a regulated cascade requiring DDK-mediated MCM4 phosphorylation, Sld3, Mcm10, TopBP1, DUE-B, and DONSON; once loaded, GINS displaces Sld3 and together with Cdc45 bridges the Mcm2–Mcm5 gate of the MCM2–7 ring, closing the channel and allosterically stimulating ATPase/helicase activity ~100-fold (PMID:20122406, PMID:21378962, PMID:21362622). Cdc45 binds single-stranded DNA through a RecJ-like DHH fold, guards leading-strand engagement within the CMG channel, catalytically loads RPA onto nascent ssDNA, and couples helicase stalling to polymerase arrest under replication stress; its ssDNA-binding activity is also required for checkpoint kinase Rad53 recruitment to limit unscheduled origin firing (PMID:24293646, PMID:25561522, PMID:28100698, PMID:23382391, PMID:30595439). Biallelic partial loss-of-function mutations in CDC45 cause Meier-Gorlin syndrome and craniosynostosis, while Cdc45 levels are rate-limiting for origin firing frequency and are regulated by Chk1, PP2A, and c-Myc (PMID:27374770, PMID:26919204, PMID:28030798, PMID:31562245, PMID:23643534).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1997 High

    Before any mechanistic understanding existed, genetic analysis established that CDC45 is an essential replication initiation gene that interacts with ORC, MCM, and the DDK kinase Cdc7/Dbf4 to trigger origin firing in late G1.

    Evidence Synthetic lethality, 2D gel electrophoresis, and epistasis analysis in S. cerevisiae

    PMID:9001208 PMID:9356482

    Open questions at the time
    • No biochemical activity defined
    • No physical interactions mapped
    • Mechanism of action at origins unknown
  2. 2000 High

    Biochemical studies in Xenopus and fission yeast revealed that Cdc45 is the first factor loaded onto origins after pre-RC assembly and is required for origin unwinding, RPA loading, and sequential recruitment of DNA polymerases alpha and epsilon, establishing a defined loading hierarchy.

    Evidence Immunodepletion, chromatin fractionation, supercoiling assays in Xenopus egg extracts; Co-IP in fission yeast

    PMID:10882098 PMID:10886370 PMID:11344166 PMID:9755170

    Open questions at the time
    • Whether Cdc45 possesses intrinsic enzymatic activity unknown
    • Factors mediating Cdc45 loading onto pre-RC not identified
  3. 2002 High

    Upstream regulators of Cdc45 loading were identified: Mcm10 acts after pre-RC formation but before Cdc45 binding, TopBP1/Xmus101 provides a parallel requirement, and PP2A dephosphorylation of a soluble factor is necessary, defining a multi-branch regulatory pathway converging on Cdc45 recruitment.

    Evidence Immunodepletion and chromatin association assays in Xenopus extracts; degron experiments in fission yeast

    PMID:11864598 PMID:12185086 PMID:12438414 PMID:12972571

    Open questions at the time
    • Identity of the PP2A substrate unknown
    • Whether TopBP1 directly contacts Cdc45 not yet tested
    • Relative ordering of Mcm10 and TopBP1 steps unclear
  4. 2006 High

    The discovery of the CMG complex (Cdc45–MCM2–7–GINS) as the replicative helicase established that Cdc45 is not merely an initiation factor but a core component of the active unwinding machine that travels with forks; DDK phosphorylation of MCM4 was shown to trigger Cdc45 chromatin association, and Chk1 checkpoint signaling suppresses it.

    Evidence Immunoaffinity purification and helicase assay from Drosophila embryos; RPC purification in yeast; Cdc7-KO and ChIP in human cells; Chk1 inhibitor rescue

    PMID:16483939 PMID:16531994 PMID:16798881 PMID:16912045 PMID:16990792 PMID:17046832

    Open questions at the time
    • Structural basis of Cdc45 within CMG unknown
    • How GINS and Cdc45 activate MCM ATPase unclear
    • Whether Cdc45 contacts DNA directly not tested
  5. 2011 High

    Structural and reconstitution studies revealed that GINS and Cdc45 bridge the Mcm2–Mcm5 gate to close the MCM ring, activating ATPase activity ~100-fold; GINS displaces Sld3 from a pre-existing Cdc45–Mcm2-7–Sld3 intermediate, defining a switch mechanism during origin activation; Cdc45 levels and Sld3/Sld7 were shown to be rate-limiting for replication timing.

    Evidence EM structure of CMG; competition assays with purified proteins; ATPase/helicase reconstitution from Drosophila CMG; ChIP and dosage experiments in yeast

    PMID:20122406 PMID:21362622 PMID:21378962 PMID:22169533

    Open questions at the time
    • Atomic-resolution structure of Cdc45 lacking
    • How Cdc45 engages DNA within the CMG channel unknown
  6. 2013 High

    Cdc45 was found to bind ssDNA (≥40 nt) with high affinity through a RecJ-like DHH fold, acting as a molecular wedge for strand displacement; a ssDNA-binding-deficient mutant caused helicase-polymerase uncoupling under replication stress, demonstrating that Cdc45's intrinsic DNA-binding activity couples fork progression to checkpoint responses.

    Evidence SPR, AFM, SAXS, gel shifts with recombinant human Cdc45; site-directed mutagenesis with ChIP and HU sensitivity in yeast

    PMID:23382391 PMID:24293646

    Open questions at the time
    • No nuclease activity confirmed despite RecJ homology
    • Whether ssDNA binding is required during normal elongation untested
  7. 2016 High

    The 2.1 Å crystal structure of human Cdc45 confirmed the RecJ/DHH fold with a blocked DNA-binding groove due to an N–C terminal intramolecular interaction; concurrently, biallelic CDC45 mutations were shown to cause Meier-Gorlin syndrome, directly linking reduced Cdc45 levels to a human developmental replication disorder.

    Evidence X-ray crystallography with mutagenesis; exome sequencing and transcript/protein quantification in patient cells

    PMID:27189187 PMID:27374770

    Open questions at the time
    • How disease mutations specifically impair CMG function not biochemically reconstituted
    • Whether craniosynostosis reflects tissue-specific Cdc45 dosage sensitivity unknown
  8. 2017 High

    Cdc45 was shown to catalytically load RPA onto nascent ssDNA through a direct Cdc45–RPA70A interaction, with RPA transitioning from 8–10 nt to 30 nt binding mode upon release; this established Cdc45 as an active RPA chaperone at the fork rather than a passive structural component.

    Evidence SPR and real-time RPA-ssDNA binding with purified human proteins

    PMID:28100698

    Open questions at the time
    • Whether RPA loading by Cdc45 is essential in vivo not demonstrated by mutant analysis
    • Structural basis of Cdc45–RPA handoff unknown
  9. 2019 High

    Cdc45 was integrated into oncogenic and checkpoint signaling: c-Myc directly interacts with Cdc45 to promote CMG assembly at Myc-targeted sites via HAT-mediated chromatin decondensation; PP2A forms a complex with CDC45 and its hyperactivation dissociates Cdc45 from replisomes causing fork collapse; Rad53/Chk2 is recruited to replisomes through Cdc45 FHA-interaction motifs to inhibit origin firing.

    Evidence Chromatin tethering, Co-IP, siRNA, and DNA fiber assays in human cells; genetic epistasis and Co-IP in yeast

    PMID:30595439 PMID:30911685 PMID:31562245

    Open questions at the time
    • Whether Rad53–Cdc45 interaction is conserved in human CHK2 not tested
    • Structural basis of PP2A–Cdc45 interaction unknown
  10. 2023 High

    DONSON was identified as a factor required for Cdc45 and GINS association with MCM2-7 during initiation, acting through CDK-dependent interaction with TopBP1, and also functioning as a replisome component during elongation.

    Evidence Immunodepletion, chromatin fractionation, Co-IP in Xenopus egg extracts

    PMID:37638758

    Open questions at the time
    • Direct DONSON–Cdc45 contact not demonstrated
    • Whether DONSON role is conserved in mammalian somatic cells not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include whether Cdc45 retains latent nuclease activity through its RecJ-like DHH domain, the structural basis for conformational changes in the Cdc45 N–C terminal block upon CMG engagement with ssDNA, and how tissue-specific Cdc45 dosage sensitivity leads to the selective skeletal phenotypes of Meier-Gorlin syndrome.
  • No nuclease activity detected despite structural homology to RecJ
  • No tissue-specific expression or dosage studies in developmental models
  • Full reconstitution of human CMG activation cascade from pre-RC to active helicase not achieved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 3 GO:0140657 ATP-dependent activity 3
Localization
GO:0005694 chromosome 4 GO:0005634 nucleus 3
Pathway
R-HSA-69306 DNA Replication 7 R-HSA-1640170 Cell Cycle 5 R-HSA-73894 DNA Repair 4 R-HSA-1643685 Disease 1
Partners
GINS (PSF2/PSF3/SLD5)MCM10MCM5MCM7MYCPOLA1RPATOPBP1
Complex memberships
CMG (Cdc45-MCM2-7-GINS)Ctf4-CMG complexSld3-Cdc45 complex

Evidence

Reading pass · 66 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 CDC45 in S. cerevisiae is essential for replication initiation and genetically interacts with ORC (orc2-1), MCM genes (mcm2-1, mcm3-1, CDC46, CDC47, CDC54), with cdc45-1 mutants showing delayed S phase entry and reduced origin firing on 2D gels. Genetic complementation, synthetic lethality analysis, 2D gel electrophoresis of replication origins, plasmid loss assays Molecular and cellular biology High 9001208
1997 CDC45 functions in late G1 phase in concert with CDC7/DBF4 kinase to trigger initiation at replication origins; Cdc45 and Cdc7/Dbf4 are mutually dependent for function. Cell cycle synchronization, genetic epistasis, functional assays in S. cerevisiae Proceedings of the National Academy of Sciences of the United States of America High 9356482
1998 Xenopus Cdc45 physically interacts with DNA polymerase alpha in egg extracts and is required for loading of DNA polymerase alpha onto chromatin at the onset of S phase, under the control of S-phase CDK activity. Co-immunoprecipitation, immunodepletion from Xenopus egg extracts, chromatin fractionation, recombinant protein addition The EMBO journal High 9755170
1998 Human CDC45 co-immunoprecipitates with ORC2L from cell extracts, and its association with the nuclear fraction becomes labile as S phase progresses. Co-immunoprecipitation, subcellular fractionation in human cells The Journal of biological chemistry Medium 9660782
1999 Human CDC45 directly binds human MCM7 and the p70 subunit of DNA polymerase alpha in vitro, suggesting it acts as a molecular tether for polymerase alpha loading onto the replication complex. In vitro direct binding assay (pull-down) European journal of biochemistry Medium 10518787
1999 CDC45 and DPB11 are required for processive DNA replication and resistance to topoisomerase I-mediated DNA damage; cdc45-10 and dpb11-10 mutants accumulate Okazaki fragments, suggesting a common role in promoting processive replication through polymerase switching. Yeast genetic screen, analysis of Okazaki fragment accumulation, synthetic lethality Proceedings of the National Academy of Sciences of the United States of America Medium 10500195
2000 Cdc45 is required for origin unwinding (negative supercoiling) in Xenopus extracts; Cdc45 binds chromatin before DNA polymerase alpha and RPA at the G1/S transition, establishing a sequential loading order: Cdc45 → RPA → DNA polymerase alpha. Plasmid supercoiling assay, immunodepletion, chromatin binding assays in Xenopus egg extracts Molecular cell High 10882098
2000 In Xenopus egg extracts, Cdc45 forms stable complexes with MCM or DNA polymerase alpha on chromatin and is essential for sequential loading of RPA, DNA polymerase alpha, and PCNA; DNA polymerase epsilon loading requires Cdc45 but not DNA polymerase alpha. Immunodepletion, chromatin fractionation, immunoprecipitation from Xenopus egg extracts Genes to cells : devoted to molecular & cellular mechanisms High 10886370
2001 CDC45 is required for postimplantation mouse development; homozygous CDC45 null embryos fail to proliferate inner cell mass cells, establishing CDC45 as essential for mammalian DNA replication in vivo. Gene targeting in mice, embryo culture, analysis of inner cell mass proliferation Molecular and cellular biology High 11416137
2001 Sld3 forms a stable complex with Cdc45 throughout the cell cycle in S. cerevisiae; origin associations of Sld3 and Cdc45 are mutually dependent; the Sld3-Cdc45 complex is required upstream of RPA loading and origin unwinding. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), genetic analysis of ts mutants in yeast The EMBO journal High 11296242
2001 Fission yeast Cdc45 (Sna41) interacts with Pol alpha throughout the cell cycle and with MCM6 (Mis5) in chromatin fractions at G1/S; in initiation-defective sna41 mutant, Pol alpha fails to associate with MCM proteins, showing Cdc45 facilitates Pol alpha loading onto MCM at origins. Co-immunoprecipitation with epitope-tagged proteins, chromatin fractionation in fission yeast The Journal of biological chemistry High 11344166
2002 Xenopus Mcm10 binding to origins requires chromatin-bound MCM2-7 and is independent of Cdk2/Cdc7; in the absence of XMcm10, XCdc45 binding, XRPA binding, and origin unwinding are blocked, placing Mcm10 after pre-RC assembly but before Cdc45 loading. Immunodepletion, chromatin binding assays, plasmid supercoiling assay in Xenopus egg extracts Molecular cell High 11864598
2002 Xenopus Xmus101 (TopBP1 homolog) is required for loading of Cdc45 onto origins; Xmus101 chromatin association depends on ORC but not on MCM2-7 or S-Cdk, defining a bifurcated pathway upstream of Cdc45 loading. Immunodepletion, chromatin binding assays in Xenopus egg extracts The Journal of cell biology High 12438414
2002 Protein phosphatase 2A (PP2A) activity is required for loading of Cdc45 onto the pre-replicative complex in Xenopus extracts; PP2A acts via dephosphorylation of a soluble factor distinct from pre-RC components or Cdc45 itself, and does not affect MCM10 loading or kinase activities. Immunodepletion, okadaic acid inhibition, chromatin binding assays in Xenopus egg extracts The Journal of biological chemistry High 12185086
2003 After DNA replication initiation in Xenopus extracts, all six MCM subunits and Cdc45 form a tight complex on chromatin in a CDK- and Cdc45-dependent manner; chromatin immunoprecipitates of this MCM-Cdc45 complex exhibit DNA helicase activity. Denaturing immunoprecipitation, chromatin immunoprecipitation, helicase assay from Xenopus egg extracts Genes to cells : devoted to molecular & cellular mechanisms High 12581157
2003 Fission yeast Cdc23/Mcm10 inactivation blocks Cdc45 chromatin binding without affecting pre-RC (Mcm2) assembly, showing Mcm10 function is required after pre-RC formation for Cdc45 loading; Cdc23 remains chromatin-bound throughout the cell cycle in fission yeast. Degron-mediated protein inactivation, cytological chromatin binding assay in fission yeast Molecular biology of the cell High 12972571
2004 MCM7 and Cdc45 are both required throughout DNA replication elongation (not just initiation) in vertebrates; both are components of the replicative helicase that unwinds DNA during replication, as shown by their requirement for aphidicolin-induced chromosome unwinding. Xenopus egg extract functional inhibition (Rb fragment, antibody neutralization), aphidicolin uncoupling assay, DNA unwinding measurement The EMBO journal High 15329670
2004 Mcm10 is involved in recruiting Cdc45 to the ARS1 pre-replication complex in S. cerevisiae; physical interaction between Cdc45 and Mcm10 is disrupted in mcm10-1 mutant, and overexpression of either suppresses the other's growth defect. ChIP at ARS1, genetic suppression analysis, co-immunoprecipitation in yeast Journal of molecular biology Medium 15201046
2005 Targeting Cdc45 to specific chromosomal sites in mammalian cells induces large-scale chromatin decondensation correlated with histone H1 phosphorylation; Cdk2 is recruited to sites of Cdc45 decondensation and physically interacts with Cdc45; Cdk2 kinase activity is required for decondensation. Lac repressor chromatin targeting, live imaging, kinase inhibition, co-immunoprecipitation in mammalian cells The Journal of cell biology High 15753125
2006 GINS is essential for maintaining the association between MCM and Cdc45 within replisome progression complexes (RPCs) at replication forks; GINS allows MCM to interact with key regulatory proteins including Cdc45, Mrc1, Tof1-Csm3, FACT, and Ctf4. Tandem affinity purification of RPCs from S. cerevisiae, mass spectrometry, genetic analysis Nature cell biology High 16531994
2006 Cdc45 exists in a stable high-molecular-weight complex with MCM2-7 and GINS (the CMG complex) in Drosophila embryo extracts; the purified CMG complex exhibits ATP-dependent DNA helicase activity; RNAi knockdown of GINS or Cdc45 blocks S-phase transition. Immunoaffinity purification from Drosophila embryo extracts, DNA helicase assay, RNAi knockdown Proceedings of the National Academy of Sciences of the United States of America High 16798881
2006 MCM2-7, Cdc45, and GINS are enriched at paused replication forks in Xenopus extracts (along with DNA polymerases, Mcm10); with aphidicolin, only Cdc45, GINS, and MCM2-7 remain at the pause site, defining the 'unwindosome' as the core helicase containing these three factors. Biotin-streptavidin fork pausing, chromatin immunoprecipitation in Xenopus egg extracts Molecular cell High 16483939
2006 Cdc7 kinase phosphorylates MCM4 N-terminal residues in MCM complexes; this phosphorylation stimulates Cdc45 association with chromatin, establishing Cdc7-mediated MCM4 phosphorylation as a trigger for Cdc45 loading at replication origins. Phospho-specific antibodies, Cdc7 knockout/siRNA cells, chromatin association assays, in vitro kinase assay The Journal of biological chemistry High 17046832
2006 In fission yeast, Sld3 loads upstream of GINS and Cdc45 at origins; GINS integrity is required for Cdc45 loading but not Sld3 loading; DDK is required for Sld3 loading while CDK is additionally required for GINS and Cdc45 loading. Chromatin immunoprecipitation with ts mutants, pull-down assays in fission yeast The EMBO journal High 16990792
2006 Chk1-dependent S-phase checkpoint reduces chromatin-associated Cdc45 levels and disrupts the Mcm7-Cdc45 interaction at replication origins following BPDE-induced DNA damage, independently of Cdc25A/Cdk2 and Cdc7/Dbf4. Chromatin fractionation, co-immunoprecipitation, chromatin immunoprecipitation, Chk1 inhibitor UCN-01 rescue, overexpression studies in human cells The Journal of biological chemistry High 16912045
2007 Human Cdc45 interacts with MCM5, MCM7, GINS subunit PSF2, and DNA polymerases delta and epsilon during S phase; Cdc45 co-localizes with active replication sites in S phase nuclei, supporting a role in elongation complex bridging. Co-immunoprecipitation, immunofluorescence co-localization in human cells Genes to cells : devoted to molecular & cellular mechanisms Medium 17573775
2008 Human TopBP1 directly interacts with Cdc45 in vitro and in vivo; BRCT domains 1, 2, and 6 of TopBP1 mediate interaction with Cdc45; overexpression of the 6th BRCT domain reduces Cdc45 chromatin loading; interaction is maximal at G1/S. GST pull-down, co-immunoprecipitation, chromatin loading assays, deletion mutant analysis in HeLa cells The Biochemical journal High 17887956
2008 Cdc45-dependent accumulation of RPA-ssDNA complexes and apoptosis following replication stress in Chk1-depleted cells can be suppressed by siRNA knockdown of Cdc45, demonstrating Cdc45 helicase activity drives RPA-ssDNA accumulation and subsequent apoptosis. siRNA knockdown, RPA foci quantification, apoptosis assays in human cells Cell death and differentiation Medium 18239674
2008 Human CDT1 associates with CDC7 kinase and recruits CDC45 to chromatin; CDC7 activity regulates the amount of CDT1 bound to chromatin, coupling CDT1 displacement with CDC45 loading. Co-immunoprecipitation, chromatin association assays, CDC7 inhibition in human cells The Journal of biological chemistry Medium 19054765
2009 Assembly of the human CMG (Cdc45-MCM2-7-GINS) complex requires CDK and Cdc7 kinase activities as well as RecQL4, Ctf4/And-1, and Mcm10; CMG interactions are detected only after the G1/S transition; surprisingly, TopBP1 depletion does not significantly affect CMG assembly in human cells. Bimolecular fluorescence complementation (BiFC), siRNA depletion, CDK inhibitor treatment in HeLa cells Proceedings of the National Academy of Sciences of the United States of America High 19805216
2009 Human GINS associates with Cdc45 and MCM2-7 in the CMG complex on chromatin specifically during S phase; hGINS down-regulation destabilizes CMG, causes G1/S arrest and slows ongoing DNA replication. Co-immunoprecipitation, chromatin fractionation, siRNA knockdown, cell cycle analysis in human cells Nucleic acids research High 19223333
2009 H3K36 methylation by Set2 regulates the timing of Cdc45 association with replication origins in S. cerevisiae; deletion of SET2 delays Cdc45 binding and renders its dynamics insensitive to histone acetylation state. Chromatin immunoprecipitation in yeast deletion mutants PloS one Medium 19521516
2010 The DNA unwinding element binding protein DUE-B interacts with Cdc45 and both localize to active replication origin DUEs; DUE-B immunodepletion from Xenopus extracts blocks replication and Cdc45 loading; DUE-B, Cdc45, and TopBP1 form complexes. Co-immunoprecipitation, ChIP at specific origins, immunodepletion from Xenopus egg extracts, baculovirus co-expression Molecular and cellular biology High 20065034
2010 Recombinant Drosophila CMG complex (Cdc45-MCM2-7-GINS) shows ATP hydrolysis rates elevated ~100-fold over MCM2-7 alone, robust helicase activity on circular templates, and improved DNA affinity; GINS binds specifically to MCM4; Cdc45 and GINS activate MCM2-7 allosterically. Reconstitution with recombinant proteins, ATPase assay, helicase assay, pairwise binding assays Molecular cell High 20122406
2011 Sld3, Sld7, and Cdc45 form a complex that associates with early-firing origins in G1 in a DDK-dependent manner; increased dosage of Sld3/Sld7/Cdc45 causes late-firing origins to fire earlier, establishing their limited association with origins as the key determinant of replication timing. ChIP, protein overexpression, genetic analysis in S. cerevisiae Current biology : CB High 22169533
2011 GINS and Sld3 compete for binding to Mcm2-7 and Cdc45; a CMS (Cdc45-Mcm2-7-Sld3) complex and CMG complex form with 1:1:1 stoichiometry; GINS displaces Sld3 from Cdc45 and Mcm2-7 binding, suggesting a switch mechanism during origin activation. In vitro binding assays with purified proteins, size exclusion chromatography, competition experiments The Journal of biological chemistry High 21362622
2011 Electron microscopy structures of MCM2-7 and CMG complex reveal that GINS and Cdc45 bridge the Mcm2-Mcm5 gap in the hexamer, forming a topologically closed ring; nucleotide binding further seals the channel; this structural mechanism explains how GINS-Cdc45 activate MCM2-7. Single-particle electron microscopy of purified CMG complex, structural analysis Nature structural & molecular biology High 21378962
2011 Sequence analysis reveals Cdc45 shares a common ancestor with bacterial/archaeal RecJ nucleases and contains a predicted DHH exonuclease domain with a catalytic site, suggesting evolutionary relationship to phosphoesterases. Computational sequence analysis (bioinformatics), phylogenomic analysis Bioinformatics (Oxford, England) Low 21653514
2011 Human Cdc45 protein has weak evolutionary relationship to DHH phosphoesterase family (including RecJ); it binds single-stranded DNA but not double-stranded DNA; SAXS data are consistent with a RecJ/DHH family fold. Bioinformatics, ssDNA binding assay, small angle X-ray scattering (SAXS) of recombinant human Cdc45 The Journal of biological chemistry Medium 22147708
2011 In budding yeast, Mcm10 is required for CMG translocation and RPA loading at origins after stable CMG assembly; auxin-inducible Mcm10 degradation allows CMG assembly but blocks subsequent translocation and origin unwinding; Mcm10 associates with origins in an S-Cdk- and Cdc45-dependent manner. Auxin-inducible degron, ChIP, checkpoint activation assay in S. cerevisiae Current biology : CB High 22285032
2012 Human CMG complex purified from Sf9 cells unwinds duplex DNA up to 500 bp, translocates 3' to 5' on the leading strand, and in combination with DNA polymerase epsilon supports rolling circle synthesis of products >10 kb. Baculovirus purification, helicase assay, rolling circle DNA synthesis assay with human CMG and Pol ε Proceedings of the National Academy of Sciences of the United States of America High 22474384
2012 Chk2 kinase, but not Chk1, directly inhibits Drosophila CMG helicase activity in vitro; Chk2 phosphorylates MCM3, MCM4, and GINS subunit Psf2; ionizing radiation induces hyperphosphorylation of Psf2 in active helicase complexes in fly embryos. In vitro kinase and helicase assay with purified Drosophila CMG, phosphatase treatment, ionizing radiation in embryos Proceedings of the National Academy of Sciences of the United States of America High 22853956
2013 Human Cdc45 binds long (≥40 nt) ssDNA with high affinity, binds 3'-protruding strands and fork/bubble/D-loop structures, slides on DNA with 3'-5' polarity, and acts as a molecular 'wedge' to initiate strand displacement; it exists as an alpha-helical monomer structurally similar to RecJ. SPR, AFM, SAXS, SRCD, gel shift assays with recombinant human Cdc45 Nucleic acids research High 24293646
2013 Cdc45 from budding yeast binds long (≥40 nt) ssDNA and this interaction specifically disrupts the Cdc45-Mcm2-7 interaction; a Cdc45 mutant unable to bind ssDNA causes helicase-polymerase uncoupling and excess RPA accumulation at origins under replication stress, demonstrating Cdc45-ssDNA interaction is required for helicase stalling during replication stress. DNA binding assays with purified protein, site-directed mutagenesis, ChIP, yeast cell growth assays under hydroxyurea The Journal of biological chemistry High 23382391
2013 c-Myc overexpression increases replication origin density and causes fork stalling/collapse; Cdc45 overexpression recapitulates all c-Myc-induced replication stress phenotypes; Cdc45 and GINS function downstream of Myc in regulating replication initiation. DNA combing, origin density analysis, DNA damage assays, epistasis by Cdc45/GINS overexpression in Xenopus extracts and human cells Cell reports High 23643534
2013 Human Ctf4 forms a homodimeric complex with the CMG helicase (hCtf4-CMG); isolated from purified proteins and from HeLa chromatin; hCtf4-CMG retains DNA helicase activity that is more salt-resistant than CMG alone; hCtf4 interacts with multiple CMG components. In vitro interaction with purified proteins, co-infection of Sf9 cells, immunoprecipitation from HeLa chromatin, helicase assay Proceedings of the National Academy of Sciences of the United States of America High 24255107
2013 Human Cdc45 interacts with all MCM2-7 subunits, PSF2, PSF3, SLD5 (GINS subunits), RPA2, AND-1, and TopBP1 by immunoprecipitation; Cdc45 chromatin association peaks at mid-S phase and a significant portion resides in non-DNA-associated nuclear scaffold. Immunoprecipitation, chromatin fractionation, nuclease treatment in synchronized HeLa cells Journal of biochemistry Medium 23364835
2013 Cdc45 interacts with Claspin, RPA, and DNA polymerase delta in a cell cycle-dependent manner maximal during S phase; UV damage reduces Cdc45-Claspin complex formation in a manner upstream of ATR activation; the C-terminal part of Cdc45 may mediate Claspin interactions. Co-immunoprecipitation, deletion mutant analysis, UV treatment, kinase inhibitors in human cells The FEBS journal Medium 23910567
2013 Human Mcm10 C-terminal domain directly binds Cdc45; Mcm10 internal domain contacts Cdc45 in a DNA-dependent manner; both Mcm10 domains enhance Cdc45 DNA-binding affinity, preferentially to bubble and fork DNA structures. Co-immunoprecipitation from cell extracts, in vitro Co-IP, surface plasmon resonance, DNA binding assays with purified proteins The Biochemical journal Medium 23750504
2015 Cdc45 guards against leading-strand slippage from the CMG central channel: cross-linking studies show the leading strand interacts with Cdc45 in the open gate (Mcm2/Mcm5 gap open) state; Cdc45 RecJ-fold mutations that abolish this interaction diminish helicase activity. Cross-linking with purified Drosophila CMG, mutagenesis, helicase assay Proceedings of the National Academy of Sciences of the United States of America High 25561522
2015 Human DNA helicase B (HDHB) directly interacts with Cdc45 via HDHB N-terminus and helicase domain binding to Cdc45 N-terminus; HDHB depletion reduces Cdc45 chromatin association, suggesting HDHB facilitates Cdc45 recruitment at G1/S. In vitro binding with purified proteins, siRNA depletion, chromatin fractionation in human cells Experimental cell research Medium 25933514
2015 Dpb11 directly binds Mcm2-7 and can recruit Cdc45 to Mcm2-7; ssDNA inhibits Dpb11-Mcm2-7 interaction; a Dpb11 mutant retaining Mcm2-7 binding in the presence of ssDNA blocks GINS-Mcm2-7 interaction during S phase and impairs RPA loading, establishing a model where Dpb11 mediates initial Cdc45 recruitment before GINS replaces it. In vitro binding with purified proteins, site-directed mutagenesis, ChIP in S. cerevisiae, genetic analysis The Journal of biological chemistry High 25659432
2016 Crystal structure of human Cdc45 at 2.1 Å confirms evolutionary link to bacterial RecJ nuclease with a DHH fold; a long-range N-C terminal interaction blocks the DNA-binding groove of its RecJ-like fold; a helical insertion appears poised for replisome interactions; mutational analysis validates mechanisms of Cdc45 association with MCM ring and GINS. X-ray crystallography at 2.1 Å, mutagenesis, structural modeling with EM data Nature communications High 27189187
2016 Biallelic loss-of-function mutations in CDC45 cause Meier-Gorlin syndrome and craniosynostosis; mutations reduce full-length CDC45 transcript and protein levels, consistent with partial loss of CDC45 function and reduced DNA replication/cell proliferation. Exome/genome sequencing, RT-PCR transcript analysis, protein quantification in patient cells American journal of human genetics High 27374770
2016 Cdc45 overexpression in human cells fires at least twice as many origins but causes ~2-fold reduced fork elongation rate, pronounced fork asymmetry, early S phase arrest, accumulation of long ssDNA stretches (replication catastrophe), and ATM/Chk2 (not ATR/Chk1) response due to RPA exhaustion. DNA fiber assay, flow cytometry, immunofluorescence, γH2AX staining, checkpoint kinase analysis in human cells overexpressing Cdc45 Cell cycle (Georgetown, Tex.) High 26919204
2016 TIMELESS (TIM) interacts with MCM2-7 prior to replication initiation; TIM depletion leads to accumulation of aberrant CMG complexes on chromatin lacking proper CDK/CDC7 phosphorylation and with reduced DNA unwinding activity. Co-immunoprecipitation, chromatin fractionation, siRNA depletion, helicase activity assay in human cell lines The Journal of biological chemistry Medium 27587400
2017 Human Cdc45 forms a complex with RPA and catalytically loads RPA onto nascent ssDNA; Cdc45-bound RPA initially complexes with ssDNA in the 8-10 nt binding mode and transitions to 30-mer mode upon release; loading requires physical contact between Cdc45 and the RPA70A subdomain. Pull-down assays, surface plasmon resonance, real-time RPA-ssDNA binding analysis with purified human proteins Nucleic acids research High 28100698
2017 Combined Wee1 and Chk1 inhibition synergistically increases CDC45 loading and S-phase DNA damage; Chk1 suppresses CDC45 loading independently of CDK activity, limiting unscheduled replication initiation despite high CDK activity when Wee1 alone is inhibited. Flow cytometry, CDC45 loading assays, S-phase DNA damage quantification with kinase inhibitors in human cells Oncotarget High 28030798
2018 Cdc45 recruits checkpoint kinase Rad53 to both replication initiation and elongation complexes via FHA-interaction motifs in an unstructured loop of Cdc45; Rad53 phosphorylates these motifs itself (autophosphorylation cascade); this interaction is required for inhibition of origin firing through Sld3 and for response to replication stress; a Meier-Gorlin syndrome Cdc45 mutation disrupts this interaction. Co-immunoprecipitation, mutant analysis, genetic epistasis, ChIP in S. cerevisiae; structural/domain analysis Molecular cell High 30595439
2019 Myc directly interacts with Cdc45 and promotes Cdc45/GINS recruitment to MCM at Myc-targeted chromosomal sites via GCN5/Tip60/TRRAP-mediated chromatin decondensation; Myc Box II is required for chromatin unfolding, Cdc45 recruitment, and CMG activation; co-expression of GCN5 or Tip60 with MBII-deficient Myc rescues these events. Lac repressor chromatin targeting, co-immunoprecipitation, siRNA knockdown, CMG assembly assays in human cells Communications biology High 30911685
2019 PP2A forms a complex with CDC45 during replication; increased PP2A activity dissociates CDC45 and polymerase alpha from the replisome, leading to fork collapse, dsDNA breaks, and a replication stress response. Chemical biology PP2A activation, genetic PP2A loss, co-immunoprecipitation with CDC45, DNA fiber assay, DSB detection in human cells The Journal of biological chemistry High 31562245
2019 DNAJA1 (a Hsp40 chaperone), activated by E2F1, stabilizes CDC45 protein; KNK437-mediated DNAJA1 inhibition reduces CDC45 levels, cell cycle progression, tumor growth and metastasis in colorectal cancer. Protein stability assays, siRNA/overexpression in cancer cells and in vivo tumor models Oncogene Medium 31477839
2019 Fkh1-driven relocalization of replication origins from the nuclear periphery to the interior in G1 requires DDK function and Cdc45 loading; Cdc45 loading correlates with increased origin mobility and nuclear interior localization. Live imaging of fluorescent lac operator-tagged origins, genetic analysis in S. cerevisiae eLife Medium 31084713
2007 Cdc45 is ubiquitylated and degraded by the proteasome pathway in differentiating human cells; Cdc45 contains putative destruction boxes and a KEN-box, suggesting it is a substrate of the APC/C. Proteasome inhibitor treatment, sequence analysis of destruction motifs in human cells Biochemical and biophysical research communications Low 17767920
2021 DDK phosphorylation of multiple sites on Mcm2-7 N-terminal tails promotes formation of Cdc45-tail-GINS (CtG) intermediates; higher CtG multiplicity (more CtGs per Mcm2-7) increases frequency of CMG formation in a second inefficient step; DDK levels modulate the number of CtGs and hence CMG formation efficiency. Single-molecule biochemical assays (TIRF microscopy), purified proteins from S. cerevisiae eLife High 33616038
2023 DONSON is required for Cdc45 and GINS association with Mcm2-7 during replication initiation in Xenopus extracts; DONSON interacts with TopBP1 in a CDK-dependent manner to facilitate CMG helicase activation; DONSON also becomes a replisome component during elongation. Immunodepletion from Xenopus egg extracts, chromatin fractionation, co-immunoprecipitation, kinase dependence analysis Nucleic acids research High 37638758

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks. Nature cell biology 614 16531994
2006 Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase. Proceedings of the National Academy of Sciences of the United States of America 560 16798881
2010 Activation of the MCM2-7 helicase by association with Cdc45 and GINS proteins. Molecular cell 452 20122406
2000 Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha. Molecular cell 335 10882098
2006 Localization of MCM2-7, Cdc45, and GINS to the site of DNA unwinding during eukaryotic DNA replication. Molecular cell 305 16483939
2011 The structural basis for MCM2-7 helicase activation by GINS and Cdc45. Nature structural & molecular biology 269 21378962
2004 A requirement for MCM7 and Cdc45 in chromosome unwinding during eukaryotic DNA replication. The EMBO journal 206 15329670
2011 Origin association of Sld3, Sld7, and Cdc45 proteins is a key step for determination of origin-firing timing. Current biology : CB 201 22169533
1998 Xenopus Cdc45-dependent loading of DNA polymerase alpha onto chromatin under the control of S-phase Cdk. The EMBO journal 195 9755170
2001 Sld3, which interacts with Cdc45 (Sld4), functions for chromosomal DNA replication in Saccharomyces cerevisiae. The EMBO journal 186 11296242
2009 Assembly of the Cdc45-Mcm2-7-GINS complex in human cells requires the Ctf4/And-1, RecQL4, and Mcm10 proteins. Proceedings of the National Academy of Sciences of the United States of America 159 19805216
2002 Xenopus Mcm10 binds to origins of DNA replication after Mcm2-7 and stimulates origin binding of Cdc45. Molecular cell 158 11864598
2006 Phosphorylation of MCM4 by Cdc7 kinase facilitates its interaction with Cdc45 on the chromatin. The Journal of biological chemistry 154 17046832
1997 CDC45, a novel yeast gene that functions with the origin recognition complex and Mcm proteins in initiation of DNA replication. Molecular and cellular biology 142 9001208
2012 Properties of the human Cdc45/Mcm2-7/GINS helicase complex and its action with DNA polymerase epsilon in rolling circle DNA synthesis. Proceedings of the National Academy of Sciences of the United States of America 113 22474384
2013 Cdc45 is a critical effector of myc-dependent DNA replication stress. Cell reports 112 23643534
2000 Central role for cdc45 in establishing an initiation complex of DNA replication in Xenopus egg extracts. Genes to cells : devoted to molecular & cellular mechanisms 112 10886370
2002 The Xenopus Xmus101 protein is required for the recruitment of Cdc45 to origins of DNA replication. The Journal of cell biology 111 12438414
2012 The CMG (CDC45/RecJ, MCM, GINS) complex is a conserved component of the DNA replication system in all archaea and eukaryotes. Biology direct 95 22329974
2005 Chromatin decondensation in S-phase involves recruitment of Cdk2 by Cdc45 and histone H1 phosphorylation. The Journal of cell biology 95 15753125
2016 Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis. American journal of human genetics 93 27374770
2012 Mcm10 plays a role in functioning of the eukaryotic replicative DNA helicase, Cdc45-Mcm-GINS. Current biology : CB 93 22285032
2003 Fission yeast Cdc23/Mcm10 functions after pre-replicative complex formation to promote Cdc45 chromatin binding. Molecular biology of the cell 89 12972571
2009 The human GINS complex associates with Cdc45 and MCM and is essential for DNA replication. Nucleic acids research 86 19223333
1997 CDC45 is required in conjunction with CDC7/DBF4 to trigger the initiation of DNA replication. Proceedings of the National Academy of Sciences of the United States of America 86 9356482
2015 Cdc45 (cell division cycle protein 45) guards the gate of the Eukaryote Replisome helicase stabilizing leading strand engagement. Proceedings of the National Academy of Sciences of the United States of America 79 25561522
2006 The Chk1-mediated S-phase checkpoint targets initiation factor Cdc45 via a Cdc25A/Cdk2-independent mechanism. The Journal of biological chemistry 79 16912045
2011 Cdc45 limits replicon usage from a low density of preRCs in mammalian cells. PloS one 75 21390258
1999 A role for the replication proteins PCNA, RF-C, polymerase epsilon and Cdc45 in transcriptional silencing in Saccharomyces cerevisiae. Genetics 75 10545450
2006 Ordered assembly of Sld3, GINS and Cdc45 is distinctly regulated by DDK and CDK for activation of replication origins. The EMBO journal 72 16990792
2016 Structure of human Cdc45 and implications for CMG helicase function. Nature communications 68 27189187
2004 Mcm10 and Cdc45 cooperate in origin activation in Saccharomyces cerevisiae. Journal of molecular biology 66 15201046
2011 Cdc45: the missing RecJ ortholog in eukaryotes? Bioinformatics (Oxford, England) 65 21653514
2003 CDK- and Cdc45-dependent priming of the MCM complex on chromatin during S-phase in Xenopus egg extracts: possible activation of MCM helicase by association with Cdc45. Genes to cells : devoted to molecular & cellular mechanisms 64 12581157
2003 A CDC45 homolog in Arabidopsis is essential for meiosis, as shown by RNA interference-induced gene silencing. The Plant cell 64 14660803
2007 Human Cdc45 is a proliferation-associated antigen. The FEBS journal 62 17608804
2016 Cdc45 is limiting for replication initiation in humans. Cell cycle (Georgetown, Tex.) 57 26919204
2007 Interactions of human Cdc45 with the Mcm2-7 complex, the GINS complex, and DNA polymerases delta and epsilon during S phase. Genes to cells : devoted to molecular & cellular mechanisms 57 17573775
2006 Cdc45-MCM-GINS, a new power player for DNA replication. Cell division 56 16930479
2019 KNK437 restricts the growth and metastasis of colorectal cancer via targeting DNAJA1/CDC45 axis. Oncogene 55 31477839
2011 Structural and functional insights into the DNA replication factor Cdc45 reveal an evolutionary relationship to the DHH family of phosphoesterases. The Journal of biological chemistry 49 22147708
2017 Combined inhibition of Wee1 and Chk1 gives synergistic DNA damage in S-phase due to distinct regulation of CDK activity and CDC45 loading. Oncotarget 48 28030798
2009 H3 k36 methylation helps determine the timing of cdc45 association with replication origins. PloS one 47 19521516
2019 Analysis of functional hub genes identifies CDC45 as an oncogene in non-small cell lung cancer - a short report. Cellular oncology (Dordrecht, Netherlands) 46 30887286
1998 The human homolog of Saccharomyces cerevisiae CDC45. The Journal of biological chemistry 46 9660782
2011 The Cdc45·Mcm2-7·GINS protein complex in trypanosomes regulates DNA replication and interacts with two Orc1-like proteins in the origin recognition complex. The Journal of biological chemistry 45 21799014
2010 The DNA unwinding element binding protein DUE-B interacts with Cdc45 in preinitiation complex formation. Molecular and cellular biology 45 20065034
1999 CDC45 and DPB11 are required for processive DNA replication and resistance to DNA topoisomerase I-mediated DNA damage. Proceedings of the National Academy of Sciences of the United States of America 45 10500195
1999 Human CDC45 protein binds to minichromosome maintenance 7 protein and the p70 subunit of DNA polymerase alpha. European journal of biochemistry 44 10518787
2013 Interaction between human Ctf4 and the Cdc45/Mcm2-7/GINS (CMG) replicative helicase. Proceedings of the National Academy of Sciences of the United States of America 43 24255107
2016 Archaeal orthologs of Cdc45 and GINS form a stable complex that stimulates the helicase activity of MCM. Proceedings of the National Academy of Sciences of the United States of America 40 27821767
2009 Regulation of Cdc45 in the cell cycle and after DNA damage. Biochemical Society transactions 37 19614620
2008 Apoptosis induced by replication inhibitors in Chk1-depleted cells is dependent upon the helicase cofactor Cdc45. Cell death and differentiation 36 18239674
2002 Protein phosphatase 2A regulates binding of Cdc45 to the prereplication complex. The Journal of biological chemistry 35 12185086
2013 Cdc45 protein-single-stranded DNA interaction is important for stalling the helicase during replication stress. The Journal of biological chemistry 33 23382391
2012 Checkpoint kinase 2 (Chk2) inhibits the activity of the Cdc45/MCM2-7/GINS (CMG) replicative helicase complex. Proceedings of the National Academy of Sciences of the United States of America 33 22853956
2013 DNA binding properties of human Cdc45 suggest a function as molecular wedge for DNA unwinding. Nucleic acids research 31 24293646
2001 Essential role of Sna41/Cdc45 in loading of DNA polymerase alpha onto minichromosome maintenance proteins in fission yeast. The Journal of biological chemistry 31 11344166
2001 Requirement of CDC45 for postimplantation mouse development. Molecular and cellular biology 31 11416137
2021 DDK regulates replication initiation by controlling the multiplicity of Cdc45-GINS binding to Mcm2-7. eLife 29 33616038
2010 Hsk1 kinase and Cdc45 regulate replication stress-induced checkpoint responses in fission yeast. Cell cycle (Georgetown, Tex.) 29 21099360
2008 Characterization of the interaction between the human DNA topoisomerase IIbeta-binding protein 1 (TopBP1) and the cell division cycle 45 (Cdc45) protein. The Biochemical journal 29 17887956
2023 DONSON facilitates Cdc45 and GINS chromatin association and is essential for DNA replication initiation. Nucleic acids research 28 37638758
2018 Helicase Subunit Cdc45 Targets the Checkpoint Kinase Rad53 to Both Replication Initiation and Elongation Complexes after Fork Stalling. Molecular cell 28 30595439
2017 The Cdc45/RecJ-like protein forms a complex with GINS and MCM, and is important for DNA replication in Thermococcus kodakarensis. Nucleic acids research 26 28977567
2017 Cdc45-induced loading of human RPA onto single-stranded DNA. Nucleic acids research 24 28100698
2011 GINS and Sld3 compete with one another for Mcm2-7 and Cdc45 binding. The Journal of biological chemistry 24 21362622
2019 Myc-driven chromatin accessibility regulates Cdc45 assembly into CMG helicases. Communications biology 23 30911685
2019 Dynamic relocalization of replication origins by Fkh1 requires execution of DDK function and Cdc45 loading at origins. eLife 21 31084713
2004 Schizosaccharomyces pombe replication protein Cdc45/Sna41 requires Hsk1/Cdc7 and Rad4/Cut5 for chromatin binding. Chromosoma 21 15338237
2015 Human DNA helicase B interacts with the replication initiation protein Cdc45 and facilitates Cdc45 binding onto chromatin. Experimental cell research 19 25933514
2013 Protein interaction and cellular localization of human CDC45. Journal of biochemistry 19 23364835
2015 Dpb11 protein helps control assembly of the Cdc45·Mcm2-7·GINS replication fork helicase. The Journal of biological chemistry 18 25659432
2013 The physical interaction of Mcm10 with Cdc45 modulates their DNA-binding properties. The Biochemical journal 18 23750504
2019 Pathogenic variants in CDC45 on the remaining allele in patients with a chromosome 22q11.2 deletion result in a novel autosomal recessive condition. Genetics in medicine : official journal of the American College of Medical Genetics 17 31474763
2016 TIMELESS Suppresses the Accumulation of Aberrant CDC45·MCM2-7·GINS Replicative Helicase Complexes on Human Chromatin. The Journal of biological chemistry 17 27587400
2017 The crystal structure of Pyrococcus furiosus RecJ implicates it as an ancestor of eukaryotic Cdc45. Nucleic acids research 16 30053256
2023 IGF2BP2 promotes glycolysis and hepatocellular carcinoma stemness by stabilizing CDC45 mRNA via m6A modification. Cell cycle (Georgetown, Tex.) 15 37985379
2022 Systematic pan‑cancer analysis identifies CDC45 as having an oncogenic role in human cancers. Oncology reports 15 36082823
2001 Sna41goa1, a novel mutation causing G1/S arrest in fission yeast, is defective in a CDC45 homolog and interacts genetically with polalpha. Molecular genetics and genomics : MGG 15 11523776
2008 Human CDT1 associates with CDC7 and recruits CDC45 to chromatin during S phase. The Journal of biological chemistry 14 19054765
2021 Knockdown of circular RNA hsa_circ_0062270 suppresses the progression of melanoma via downregulation of CDC45. Histology and histopathology 13 34931691
2013 Cell cycle-dependent formation of Cdc45-Claspin complexes in human cells is compromized by UV-mediated DNA damage. The FEBS journal 13 23910567
1998 Direct selection of conserved cDNAs from the DiGeorge critical region: isolation of a novel CDC45-like gene. Genome research 13 9724329
2022 High abundance of CDC45 inhibits cell proliferation through elevation of HSPA6. Cell proliferation 12 35642733
2021 A synonymous variant in a non-canonical exon of CDC45 disrupts splicing in two affected sibs with Meier-Gorlin syndrome with craniosynostosis. European journal of medical genetics 12 33639314
2020 RYBP inhibits esophageal squamous cell carcinoma proliferation through downregulating CDC6 and CDC45 in G1-S phase transition process. Life sciences 12 32209426
2019 Protein phosphatase 2A controls ongoing DNA replication by binding to and regulating cell division cycle 45 (CDC45). The Journal of biological chemistry 12 31562245
2012 Cell cycle-dependent mobility of Cdc45 determined in vivo by fluorescence correlation spectroscopy. PloS one 12 22536402
2020 DNA replication protein Cdc45 directly interacts with PCNA via its PIP box in Leishmania donovani and the Cdc45 PIP box is essential for cell survival. PLoS pathogens 11 32413071
1999 UFD1L and CDC45L: a role in DiGeorge syndrome and related phenotypes? Trends in genetics : TIG 11 10390621
2021 CDC45 modulates MCM7 expression and inhibits cell proliferation by suppressing the PI3K/AKT pathway in acute myeloid leukemia. American journal of translational research 10 34650692
2016 Structural insights into Cdc45 function: was there a nuclease at the heart of the ancestral replisome? Biophysical chemistry 8 27919598
2008 A kinetoplastid BRCA2 interacts with DNA replication protein CDC45. International journal for parasitology 8 18723021
2001 A common cis-acting sequence in the DiGeorge critical region regulates bi-directional transcription of UFD1L and CDC45L. Mechanisms of development 8 11578863
2024 CDC45 promotes the stemness and metastasis in lung adenocarcinoma by affecting the cell cycle. Journal of translational medicine 7 38589907
2007 Cdc45 degradation during differentiation and apoptosis. Biochemical and biophysical research communications 7 17767920
2001 Characterization of the bi-directional transcriptional control region between the human UFD1L and CDC45L genes. Biochemical and biophysical research communications 6 11341762
2018 Cdc45/Mcm2-7/GINS complex down-regulation mediates S phase arrest in okadaic acid-induced cell damage. Toxicon : official journal of the International Society on Toxinology 5 30003918
2019 Initiation-specific alleles of the Cdc45 helicase-activating protein. PloS one 4 30913274