Affinage

CDT1

DNA replication factor Cdt1 · UniProt Q9H211

Length
546 aa
Mass
60.4 kDa
Annotated
2026-06-09
100 papers in source corpus 58 papers cited in narrative 56 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDT1 is an essential DNA replication licensing factor that acts in G1 to load the MCM2-7 replicative helicase onto origins, thereby coupling S phase to mitosis in the cell-division cycle (PMID:8313888, PMID:10766248, PMID:11896191). Working together with ORC, Cdc6, and the MCM2-7 hexamer, CDT1 assembles prereplicative complexes; structural studies of the ORC-Cdc6-Cdt1-MCM2-7 (OCCM) intermediate show that CDT1 embraces MCM2, MCM4, and MCM6 (nearly half the hexamer), destabilizes the Mcm2-5 interface, and inhibits MCM ATPase to brace the ring open for DNA entry until ORC-Cdc6-triggered ATP hydrolysis drives ring closure and CDT1 ejection (PMID:28191893, PMID:28643783, PMID:28191894, PMID:23851460). CDT1 contacts MCM through its C-terminal winged-helix domain and the Mcm6 Cdt1-binding domain, an interaction governed by charge complementarity and essential for MCM chromatin loading (PMID:19722278, PMID:20202939, PMID:22140117, PMID:18606811, PMID:18006685). After origin firing CDT1 directly suppresses CMG helicase activity, so DNA synthesis begins only once CDT1 is degraded, separating licensing from synthesis (PMID:36608667). To prevent re-replication, CDT1 abundance is restricted by two redundant E3 ligases: CRL4-DDB1(CDT2), which destroys CDT1 on chromatin via a PCNA-docking PIP-box, and SCF-Skp2, which acts after CDK phosphorylation at T29/the Cy-motif, with additional control by APC/C(Cdh1) (PMID:16482215, PMID:16949367, PMID:16362051, PMID:15004027, PMID:14993212, PMID:18162579). The inhibitor geminin binds CDT1 and blocks MCM access, switching between a permissive heterotrimer and an inhibitory heterohexamer (PMID:11125146, PMID:15286659, PMID:19906994). CDT1 activity is further tuned by stress-activated p38/JNK phosphorylation that stabilizes it against CRL4(CDT2), by KAT2B/KAT3B acetylation opposed by HDAC11, by p97/CDC-48-mediated extraction of ubiquitinated CDT1 from chromatin, and by the deubiquitinase USP37 (PMID:21930785, PMID:21856198, PMID:19276081, PMID:21981919, PMID:21981920, PMID:27296872). Beyond licensing, CDT1 localizes to kinetochores in mitosis via the Hec1 loop of the Ndc80 complex to support stable kinetochore-microtubule attachments (PMID:22581055).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1994 High

    Established CDT1 as an essential gene whose loss blocks DNA replication while leaving mitotic events intact, defining its role in the S-phase–mitosis dependency relationship.

    Evidence Cdc10-bound genomic isolation and null allele phenotyping in fission yeast

    PMID:8313888

    Open questions at the time
    • Molecular function at origins not yet defined
    • No partners identified
  2. 2002 High

    Defined CDT1's core molecular activity: cooperating with Cdc6 to load MCM2-7 onto chromatin during pre-RC assembly, required for initiation but not elongation, across yeast and human cells.

    Evidence Re-replication and chromatin fractionation in S. pombe, conditional depletion in budding yeast, antibody microinjection in human cells

    PMID:10766248 PMID:11836525 PMID:11896191 PMID:11967159

    Open questions at the time
    • Structural basis of MCM loading not resolved
    • Stoichiometry of CDT1 at origins unknown
  3. 2001 High

    Identified geminin as a direct CDT1 inhibitor that suppresses replication licensing, establishing the key negative regulator of CDT1 activity.

    Evidence Xenopus egg extract replication/licensing assays, co-IP, RLF-B purification, geminin immunodepletion rescue

    PMID:11125146 PMID:11175741

    Open questions at the time
    • Structural mechanism of inhibition not yet known
    • Whether geminin blocks MCM or DNA binding unclear at this stage
  4. 2004 High

    Resolved CDT1 domain architecture and the structural basis of geminin inhibition: a geminin coiled-coil dimer contacts both CDT1 termini and sterically blocks MCM access, with separable geminin-, MCM6-, and DNA-binding regions.

    Evidence Yeast two-hybrid/domain mapping in mouse Cdt1; crystal structures of geminin–Cdt1 and geminin with mutagenesis and replication assays

    PMID:12192004 PMID:15260975 PMID:15286659

    Open questions at the time
    • Quaternary heterohexamer switch not yet appreciated
    • MCM-bound CDT1 structure absent
  5. 2006 High

    Delineated the dual proteolytic control of CDT1: CRL4-DDB1(CDT2) recognizing the PCNA-docking N-terminus and SCF-Skp2 acting after CDK phosphorylation, with APC/C(Cdh1) as a third ligase, preventing re-replication.

    Evidence Phosphorylation/kinase assays, PIP-box and destruction-box mutagenesis, in vivo/in vitro ubiquitination, co-silencing of Cul4/DDB1/Cdt2/Skp2, Xenopus extracts, zebrafish epistasis

    PMID:12840033 PMID:14578910 PMID:14993212 PMID:15004027 PMID:15448697 PMID:15598982 PMID:16362051 PMID:16482215 PMID:16861906 PMID:16949367 PMID:17085480 PMID:18162579

    Open questions at the time
    • Quantitative contribution of each ligase across cell-cycle phases not fully partitioned
    • Conjugating-enzyme specificity only partly mapped
  6. 2007 High

    Established that dynamic CDT1–ORC and CDT1–chromatin associations enable iterative MCM loading and that CDT1 recruits chromatin remodeling/acetylation activity to origins.

    Evidence In vitro helicase loading with Orc6-Cdt1 fusion, FRAP live-cell imaging, co-IP with HBO1/SNF2H/GRWD1, ChIP, MCM loading assays

    PMID:17318181 PMID:18006685 PMID:18832067 PMID:21937426 PMID:25990725

    Open questions at the time
    • In vivo necessity of chromatin remodelers for licensing varies between studies
    • Some remodeler links rest on single-lab data
  7. 2009 High

    Refined regulation of CDT1 by acetylation (KAT2B/KAT3B vs HDAC11) and by a geminin quaternary-state switch (permissive heterotrimer vs inhibitory heterohexamer) controlling licensing competence.

    Evidence In vitro acetylation/deacetylation and ubiquitylation assays; crystallography and SAXS of Cdt1–geminin complexes with functional assays

    PMID:19276081 PMID:19906994 PMID:20980834

    Open questions at the time
    • Acetylation switch not independently replicated
    • In vivo prevalence of heterohexamer vs heterotrimer not quantified
  8. 2011 High

    Showed stress-kinase and p97-based control: p38/JNK phosphorylation at T29 stabilizes CDT1 by blocking Cdt2 binding while blocking origin firing, and p97/CDC-48-UFD1/NPL4 extracts ubiquitinated CDT1 from chromatin for degradation, coordinating helicase release.

    Evidence In vitro kinase assays, ChIP, mutagenesis, genome-wide siRNA screen, Xenopus chromatin extraction, C. elegans RNAi

    PMID:21856198 PMID:21930785 PMID:21981919 PMID:21981920

    Open questions at the time
    • Physiological stresses engaging this branch incompletely defined
    • Cross-talk with the CRL4(CDT2) pathway not fully integrated
  9. 2012 High

    Revealed a non-licensing mitotic role: CDT1 binds the Hec1 loop of the Ndc80 complex at kinetochores to stabilize kinetochore-microtubule attachments and satisfy the spindle-assembly checkpoint.

    Evidence G2-specific siRNA depletion, co-IP, super-resolution microscopy, kinetochore-microtubule attachment assays

    PMID:22581055

    Open questions at the time
    • How licensing and kinetochore functions are temporally separated unclear
    • Regulation of CDT1 at kinetochores not defined
  10. 2017 High

    Provided the near-atomic mechanism of licensing: CDT1 wraps MCM2/4/6, holds the Mcm2-5 gate open, inhibits MCM ATPase, and is ejected upon ORC-Cdc6-driven ATP hydrolysis and ring closure.

    Evidence Cryo-EM of OCCM on DNA at 3.9 Å, crystallography/EM with in vitro ATPase and MCM loading reconstitution

    PMID:23851460 PMID:28191893 PMID:28191894 PMID:28643783

    Open questions at the time
    • Dynamics of the loading-to-firing transition partially inferred
    • Mammalian OCCM structural detail less complete than yeast
  11. 2023 High

    Demonstrated that CDT1 directly inhibits the CMG helicase after origin firing, so DNA synthesis begins only upon CDT1 degradation—separating licensing from synthesis rather than strictly from firing.

    Evidence In vitro reconstitution with purified human CMG and CDT1, biochemical helicase assays, quantitative single-cell microscopy

    PMID:36608667

    Open questions at the time
    • Structural basis of CDT1–CMG inhibition not resolved
    • How this overlap window is regulated in vivo unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many post-translational inputs (ubiquitination, phosphorylation, acetylation, deubiquitination, stress kinases) are integrated quantitatively to set CDT1 levels through the cycle, and the structural basis of CDT1's direct CMG inhibition, remain unresolved.
  • No unified quantitative model of competing ligases and stabilizers
  • No structure of the CDT1–CMG inhibitory complex
  • Coordination of mitotic kinetochore role with licensing unaddressed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0003677 DNA binding 2
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 3
Pathway
R-HSA-69306 DNA Replication 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 2
Partners
CDC6DDB1GEMININMCM2MCM6ORC6PCNASKP2
Complex memberships
CRL4-DDB1(CDT2) E3 ligase substrateCdt1-MCM2-7 (Cdt1-MCM heptamer)Cdt1-geminin heterohexamerpre-replicative complex (ORC-Cdc6-Cdt1-MCM2-7 / OCCM)

Evidence

Reading pass · 56 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 CDT1 (cdt1) was identified as an essential target gene of the fission yeast Cdc10/Sct1 transcription factor; cells carrying a null allele of cdt1 are defective in DNA replication but still initiate mitotic events, establishing cdt1 as essential for the S phase–mitosis dependency relationship. Immunoprecipitation-PCR to isolate Cdc10-bound genomic sequences; null allele analysis showing DNA replication defect without mitotic block The EMBO journal High 8313888
2000 Fission yeast Cdt1 is located in the nucleus, cooperates with Cdc18/Cdc6 to load the MCM protein Cdc21 onto chromatin at the end of mitosis, and both factors are required to initiate DNA replication; overexpression of both together drives extensive re-replication. Re-replication assay in S. pombe; chromatin fractionation; nuclear localization by microscopy; genetic epistasis Nature High 10766248
2000 Geminin binds tightly to Cdt1, and excess Cdt1 reverses geminin-mediated inhibition of DNA replication in cell-free Xenopus extracts, establishing that geminin inhibits replication by targeting Cdt1. Cell-free Xenopus egg extract DNA replication assay; co-immunoprecipitation; rescue by excess Cdt1 Science High 11125146
2001 RLF-B (replication licensing factor B) was purified and shown to correspond to Cdt1; geminin inhibits RLF-B/Cdt1 activity, and immunodepletion of geminin from metaphase Xenopus extracts allows assembly of licensed replication origins. Protein purification from Xenopus egg extracts; immunodepletion; replication licensing assay Nature cell biology High 11175741
2001 Human Cdt1 (hCdt1) is a nuclear protein present only in G1; after S-phase onset its levels decrease via proteasomal proteolysis (not transcriptional changes), and hCdt1 can associate with geminin. Cell cycle synchronization; immunoblotting; proteasome inhibitor stabilization; co-immunoprecipitation The Journal of biological chemistry High 11555648
2002 Budding yeast Cdt1 (Tah11/Sid2) is required for pre-RC assembly; depletion blocks Mcm2 chromatin loading and replication initiation but not elongation; Cdt1 accumulates in the nucleus during G1 and is excluded later by CDKs, and its nuclear accumulation is interdependent with Mcm2-7. Conditional depletion; chromatin fractionation; co-immunoprecipitation; cell cycle analysis Nature cell biology / Current biology High 11836525 11967159
2002 Mouse Cdt1 binds geminin through its central region (aa 177–380) and MCM6 through its C-terminal region (aa 407–477); Cdt1 also has intrinsic sequence-, strand-, and conformation-independent DNA binding activity that overlaps the geminin binding domain and is inhibited by geminin. Yeast two-hybrid; in vitro binding assays with purified proteins; domain deletion mapping The Journal of biological chemistry High 12192004
2002 Human Cdt1 is essential for DNA replication in intact human cells; it functions during the pre-RC formation window and is required for loading MCM proteins onto chromatin. Antibody microinjection into human cells; MCM chromatin loading assay Journal of cell science High 11896191
2003 The SCF(Skp2) complex ubiquitinates Cdt1 in a phosphorylation-dependent manner; Skp2 specifically interacts with Cdt1, and downregulation of Skp2 or disruption of the Cdt1–Skp2 interaction stabilizes and accumulates Cdt1. Co-immunoprecipitation; in vitro and in vivo ubiquitination assay; siRNA knockdown; dominant-negative disruption The Journal of biological chemistry High 12840033
2003 Cdc6 physically associates with Cdt1 via its N-terminal noncatalytic domain; geminin inhibits Cdt1 by blocking its binding to both Mcm2 and Cdc6; the Cdt1–Mcm2 association is regulated by cell growth and induced by Cdc6 expression. Co-immunoprecipitation; ectopic expression in quiescent cells; domain mapping The Journal of biological chemistry Medium 14672932
2003 CDT1 is rapidly degraded after UV or gamma-irradiation via the CUL4-ROC1 E3 ubiquitin ligase and the COP9 signalosome; loss of either complex completely suppresses CDT1 proteolysis; CDT1 is specifically polyubiquitinated by CUL4 complexes. siRNA knockdown of CUL4, ROC1, CSN components; in vivo ubiquitination assay; irradiation-induced degradation assay Nature cell biology High 14578910
2004 Crystal structure of the mouse geminin–Cdt1 complex reveals that a coiled-coil dimer of geminin interacts with both N-terminal and C-terminal portions of Cdt1; the primary interface involves steric complementarity with Pro181, Ala182, Tyr183, Phe186, and Leu189 of Cdt1, and the C-terminal region of geminin sterically blocks MCM access to Cdt1. X-ray crystallography; mutagenesis; biochemical binding assays Nature High 15286659
2004 DDB1 associates stoichiometrically with CUL4A in vivo; recombinant DDB1 and CDT1 bind directly in vitro; DDB1 bridges CDT1 to CUL4A in vivo; silencing DDB1 prevents UV-induced CDT1 degradation and CUL4A-mediated CDT1 ubiquitination in vitro, establishing DDB1 as the substrate adaptor for CUL4A-mediated CDT1 ubiquitination. Co-immunoprecipitation; in vitro direct binding with purified recombinant proteins; in vitro ubiquitination assay; siRNA knockdown Nature cell biology High 15448697
2004 Cdt1 is completely degraded by ubiquitin-mediated proteolysis during the first round of DNA replication in Xenopus egg extracts; degradation requires Cdk2/Cyclin E, Cdc45, RPA, and polymerase alpha (i.e., replication initiation); Cdt1 is ubiquitinated on chromatin. Xenopus egg extract replication assay; immunodepletion of replication factors; ubiquitination assay on chromatin Genes & development High 15598982
2004 Human Cdt1 is phosphorylated by Cdk2 and Cdk4; phosphorylation at a cyclin-binding motif promotes Skp2 binding and subsequent SCF(Skp2)-mediated degradation; CDK inhibitors (p21, p27) suppress Cdt1 phosphorylation and stabilize it; a quadruple Cdk-binding site mutant fails to bind Skp2 and is more stable. In vitro kinase assay; co-immunoprecipitation; site-directed mutagenesis; overexpression of CDK inhibitors The Journal of biological chemistry High 14993212 15004027
2004 Cyclin A-dependent CDK phosphorylation of Cdt1 (dependent on its cyclin-binding motif) promotes Skp2 binding and degradation, and also inhibits Cdt1 DNA-binding activity in vitro; however, geminin binding to Cdt1 is not affected by phosphorylation; inactivation of Cdk1 in G2/M leads to Cdt1 dephosphorylation and re-binding to chromatin. In vitro kinase assay; co-immunoprecipitation; in vitro DNA binding assay; synchronization of FT210 cells The Journal of biological chemistry High 14993212
2004 Geminin forms a parallel coiled-coil homodimer; point mutations disrupting dimerization abolish Cdt1 interaction and replication inhibition; a bipartite interface exists—an array of glutamic acid residues on the coiled-coil surface contacts positive charges in the middle of Cdt1, and an adjoining region independently contacts the N-terminal 100 residues of Cdt1; both interactions are essential for replication inhibition. X-ray crystallography of geminin; mutagenesis; in vitro replication assay; binding assays Molecular cell High 15260975
2004 Human Geminin protects CDT1 from proteasome-mediated degradation (by inhibiting its ubiquitination) during S phase and allows CDT1 accumulation during mitosis, establishing a positive role for Geminin in CDT1 stability; CDK1 inhibition in mitosis, not Geminin depletion, is sufficient for premature pre-RC formation in human cells. siRNA depletion; ubiquitination assay; cell synchronization; immunoblotting The EMBO journal High 15257290
2004 Cdt1 proteolysis during S phase in mammalian cells occurs through the N-terminal region (not through geminin binding), is ubiquitin-dependent, and occurs independently of geminin; the N terminus is required for nuclear localization and cyclin A association but is dispensable for geminin association; N-terminus-truncated Cdt1 is stable in S phase. In vivo ubiquitination assay; siRNA for geminin; temperature-sensitive cell lines; domain truncation analysis The Journal of biological chemistry High 15138268
2005 Replication-dependent proteolysis of Cdt1 in Xenopus egg extracts requires Cdt1 interaction with PCNA through a consensus PIP-box motif; removal of PCNA inhibits Cdt1 destruction; DDB1 (Cul4 E3 component) chromatin loading depends on Cdt1–PCNA binding; mutation of the PIP-box yields stabilized Cdt1 that induces re-replication. Xenopus egg extract replication assay; PIP-box mutagenesis; PCNA depletion; chromatin fractionation; re-replication assay Nature cell biology High 16362051
2005 Threonine 29 within the N terminus of Cdt1 is phosphorylated by Cdk2 and required for Skp2 interaction; however, T29 and the Cy motif are not necessary for S-phase proteolysis—a Skp2-independent pathway requiring the first 32 residues of Cdt1 is critical for degradation during S phase and is necessary for normal S-phase progression. Phosphopeptide mapping; mutagenesis; co-immunoprecipitation; cell cycle analysis The Journal of biological chemistry High 15855168
2006 Two distinct E3 ubiquitin ligases regulate human Cdt1 proteolysis: DDB1-Cul4 recognizes the first ~10 amino acids (six conserved residues required for PCNA binding); SCF-Skp2 recognizes a Cy-motif region after cyclin E/A-CDK phosphorylation. Both are redundantly required in S-G2; PCNA is essential for Cul4- but not Skp2-directed degradation. Domain mutagenesis; siRNA co-silencing of Skp2 and Cul4; in vivo ubiquitination assay; PCNA binding assay The EMBO journal High 16482215
2006 DCAF2/Cdt2 (a WD40 protein) functions as the substrate receptor of the CUL4-DDB1 E3 ligase to destroy Cdt1 in S phase and after DNA damage in both Xenopus and human cells; depletion of Cdt2 causes rereplication and checkpoint activation; in Xenopus, Cdt2 is recruited to replication forks via Cdt1 and PCNA, where Cdt1 ubiquitylation occurs. Identification by affinity chromatography/MS; siRNA depletion; cell cycle analysis; Xenopus egg extract assay; chromatin fractionation Molecular cell High 16949367
2006 The N-terminal region of Cdt1 contains a PCNA interaction motif required for N-terminal ubiquitination by Cul4/DDB1 after DNA damage and in S phase; the CDK2/Skp2 pathway is not essential for S-phase degradation. Domain mutagenesis; siRNA knockdown of Cul4, DDB1; in vivo ubiquitination assay; PCNA binding assay The Journal of biological chemistry High 16407252
2006 L2DTL/CDT2 associates with CUL4, DDB1, and PCNA; loss of L2DTL suppresses CDT1 proteolysis after DNA damage; PCNA loss also suppresses CDT1 proteolysis; inactivation of L2DTL dissociates DDB1 from the CUL4 complex in vivo. Anti-CUL4 affinity chromatography/MS; co-immunoprecipitation; siRNA knockdown; PCNA silencing Cell cycle High 16861906
2006 DTL/CDT2 is required for CDT1 downregulation in unperturbed cells and following DNA damage via the CUL4-DDB1 complex; cell cycle defects of Dtl-deficient zebrafish are suppressed by reducing Cdt1 levels (genetic epistasis). Zebrafish genetic screen; siRNA in human cells; genetic epistasis (Cdt1 knockdown suppresses Dtl phenotype); co-immunoprecipitation Genes & development High 17085480
2007 Orc6 directly binds Cdt1 through two regions; ORC lacking Orc6 fails to interact with Cdt1 and cannot load Mcm2-7 onto origin DNA; a fusion protein linking Cdt1 to the Orc6-CTD restores single-round Mcm2-7 loading, showing that dynamic Cdt1–ORC association is required for multiple rounds of loading. In vitro helicase-loading assay with purified proteins; direct binding assay; Orc6-Cdt1 fusion protein reconstitution Genes & development High 18006685
2007 Cdt1 associates dynamically with chromatin throughout G1 (shown by FRAP); Cdt1 simultaneously binds geminin and chromatin in vivo (contrary to in vitro data) and recruits geminin onto chromatin; chromatin-binding and geminin-binding domains are separable. Quantitative fluorescence microscopy (FRAP); domain mapping; live-cell imaging in human cells The EMBO journal High 17318181
2007 APC/C(Cdh1) is a third ubiquitin ligase that controls Cdt1 levels via three destruction boxes in the Cdt1 N-terminus; elimination of these boxes causes strong rereplication and chromosomal damage; Cdt1 also interacts with SNF2H, topoisomerases I and IIα, and GRWD1/WDR28. Cdt1 affinity chromatography/MS; co-immunoprecipitation; destruction box mutagenesis; rereplication assay Molecular biology of the cell High 18162579
2008 HBO1 histone acetylase directly interacts with Cdt1; HBO1 associates with replication origins during G1 in a Cdt1-dependent (but Geminin-independent) manner; HBO1 enhances Cdt1-dependent rereplication, establishing HBO1 as a coactivator of the Cdt1 licensing factor at origins. Co-immunoprecipitation; chromatin immunoprecipitation; rereplication assay; siRNA depletion Genes & development High 18832067
2008 MCM9 forms a stable complex with Cdt1 and is required for Mcm2-7 chromatin loading; MCM9 prevents excess geminin on chromatin during licensing, functioning as an activating linker between Cdt1 and Mcm2-7. Co-immunoprecipitation; immunodepletion in Xenopus extracts; chromatin fractionation; DNA replication assay Molecular cell High 18657502
2008 Cdt1 forms a stable complex with Mcm4/6/7 and Mcm2/3/4/5/6/7 via interaction with Mcm2 and Mcm4/6; Cdt1 stimulates DNA binding and helicase activity of Mcm4/6/7 in vitro; a Cdt1 mutant failing to stimulate helicase activity shows reduced MCM interaction and is deficient in forming the high-MW MCM-Cdt1 assembly. Glycerol gradient fractionation with purified proteins; in vitro DNA binding and helicase assay; mutagenesis The Journal of biological chemistry High 18606811
2009 Cdt1 undergoes acetylation at its N terminus by KAT2B and KAT3B; HDAC11 directly binds and deacetylates Cdt1; acetylation protects Cdt1 from ubiquitylation and proteasomal degradation. Co-immunoprecipitation; in vitro acetylation assay; HDAC11 binding assay; ubiquitylation assay The Journal of biological chemistry Medium 19276081
2009 The human Cdt1–Geminin complex can exist as a 'permissive' heterotrimer or an 'inhibitory' heterohexamer; specific Cdt1 residues buried in the heterohexamer are important for licensing; the quaternary-state switch between forms represents a molecular switch between licensing-competent and -defective states. X-ray crystallography; small-angle X-ray scattering; functional assays in Xenopus and mammalian cells; mutagenesis Proceedings of the National Academy of Sciences High 19906994
2009 The C-terminal domain of Cdt1 adopts a winged-helix fold; the winged helix is also conserved in the middle domain; structural analysis defines a binding site for the MCM complex within the C-terminal winged-helix domain. X-ray crystallography; solution NMR spectroscopy; biochemical binding analysis Protein science High 19722278
2010 The C-terminal domain of human Mcm6 is the Cdt1-binding domain (CBD); its NMR structure reveals a winged-helix fold; the helix-turn-helix motif of CBD mediates the Cdt1–Mcm6 interaction; charge complementarity is a key determinant for the Cdt1–Mcm2-7 interaction; disruption of the interaction in yeast is lethal and prevents MCM2 chromatin loading. NMR structure determination; site-directed mutagenesis; yeast in vivo MCM loading and viability assay The Journal of biological chemistry High 20202939 22140117
2010 Cdt1 induces large-scale chromatin decondensation required for MCM recruitment during G1; this requires HBO1 HAT activity and histone H4 modifications; HDAC11 inhibits Cdt1-induced chromatin unfolding and binds Cdt1 more efficiently in the presence of Geminin; the process is suppressed by Geminin. Live-cell imaging of large-scale chromatin unfolding; MCM loading assay; HBO1 and HDAC11 overexpression/knockdown Cell cycle Medium 20980834
2011 p97 AAA+-ATPase and its cofactor UFD1 are required for proteasome-dependent removal of ubiquitinated CDT1 (and SET8) from chromatin and their subsequent degradation, both in vivo and in Xenopus egg extracts; a genome-wide siRNA screen also identified nucleotide excision repair factors as promoting CDT1 destruction by recruiting PCNA to damaged DNA. Genome-wide siRNA screen; Xenopus egg extract in vitro chromatin extraction assay; immunoprecipitation Molecular cell High 21981919 21981920
2011 CDC-48/p97 and its cofactors UFD-1/NPL-4 coordinate CDT-1 degradation with release of the CDC-45/GINS complex from chromatin; C. elegans embryos lacking CDC-48 accumulate CDT-1 on mitotic chromatin and show persistent CDC-45/GINS chromatin association that is a consequence of CDT-1 stabilization. C. elegans RNAi; chromatin fractionation; Xenopus egg extract confirmation Molecular cell High 21981920
2011 CRL4(Cdt2) uses two different ubiquitin-conjugating enzymes for different substrates: UBCH8 ubiquitylates p21 and Set8, while UBE2G1/UBE2G2 polyubiquitylate Cdt1 post-radiation. Proteomic analysis of Cdt2-associated proteins; siRNA screening; in vitro and in vivo ubiquitination assays Molecular and cellular biology High 21628527
2011 SNF2H chromatin remodeler is recruited to replication origins in a Cdt1-dependent manner; SNF2H physically interacts with Cdt1; SNF2H silencing prevents MCM loading at origins and inhibits S-phase progression. Co-immunoprecipitation; chromatin immunoprecipitation; siRNA knockdown; MCM loading assay The Journal of biological chemistry Medium 21937426
2011 JNK phosphorylates Cdt1 on threonine 29 in response to non-genotoxic stress, leading to rapid dissociation of HBO1 from replication origins and blocking initiation of DNA replication; upon stress relief, HBO1 reassociates with origins. In vitro kinase assay; chromatin immunoprecipitation; mutagenesis; siRNA Molecular cell High 21856198
2011 Stress-activated MAP kinases p38 and JNK phosphorylate Cdt1 during G2 phase and acute stress; phosphorylation renders Cdt1 resistant to ubiquitin-mediated degradation by blocking Cdt1 binding to the CUL4 adaptor Cdt2; phosphomimetic mutations reduce Cdt1's ability to support origin licensing. In vitro kinase assay; co-immunoprecipitation; mutagenesis; cell synchronization; ubiquitination assay Molecular and cellular biology High 21930785
2011 Multiple Cdt1 molecules are recruited to each origin by ORC and Cdc6 during helicase loading; disruption of this multi-Cdt1 intermediate prevents Mcm2-7 loading; the C-terminus of Cdt1 binds Mcm2-7 and is required for origin recruitment; the essential N-terminal domain of Cdt1 is required to load Mcm2-7 competent for subsequent replication initiation. In vitro helicase-loading assay with purified yeast proteins; domain mutation analysis; quantitative biochemistry The EMBO journal High 22045335
2011 Cdt1 is dynamically recruited to sites of DNA damage (laser nanosurgery) in G1 phase within seconds, dependent on PCNA; PCNA and Cdt2 recruitment to damage are independent of Cdt1; PCNA provides an immobile binding interface for dynamic Cdt1 interactions that precede its degradation. Laser nanosurgery; live-cell fluorescence microscopy; FRAP with reaction-diffusion modeling; siRNA knockdown Journal of cell science High 21224399
2012 Human Cdt1 localizes to kinetochores during mitosis through direct interaction with the loop domain of Hec1 (Ndc80 complex); G2-specific Cdt1 depletion causes unstable kinetochore-microtubule attachments and Mad1-dependent spindle-assembly checkpoint arrest; Cdt1 binding to the Hec1 loop promotes a microtubule-dependent conformational change in the Ndc80 complex. G2-specific siRNA depletion; co-immunoprecipitation; super-resolution fluorescence microscopy; kinetochore-microtubule attachment assay Nature cell biology High 22581055
2012 FOXO3 forms a protein complex with Cdt1 that blocks Cdt1 interaction with DDB1 and PCNA; FOXO3 depletion facilitates Cdt1 proteolysis in unperturbed cells and impairs S-phase entry. Co-immunoprecipitation; FOXO3 siRNA; S-phase entry assay; competition binding assay Proceedings of the National Academy of Sciences Medium 22451935
2013 Cryo-EM structure of the ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) intermediate shows that ORC-Cdc6 N-terminal AAA+ domains latch onto Mcm2-7 C-terminal AAA+ domains; ORC-Cdc6 adopts a right-handed spiral with helical symmetry matching the DNA double helix, resembling the RFC clamp loader. Cryo-electron microscopy; in vitro assembly with purified components and ATPγS Nature structural & molecular biology High 23851460
2014 SCF-FBXO31 E3 ligase interacts with Cdt1 and ubiquitylates it specifically in G2 phase, independently of the previously described S-phase degradation pathways; FBXO31 depletion stabilizes Cdt1 and causes re-replication. Co-immunoprecipitation; in vitro ubiquitylation assay; cell cycle synchronization; siRNA knockdown; re-replication assay The Journal of biological chemistry Medium 24828503
2015 GRWD1 is a histone-binding protein recruited to replication origins in a CDC6- and Cdt1-dependent manner during G1; GRWD1 depletion reduces MCM loading; GRWD1 regulates chromatin openness at origin-proximate loci. Chromatin immunoprecipitation-seq; FAIRE-seq; siRNA depletion; MCM loading assay; histone-binding assay Nucleic acids research Medium 25990725
2016 USP37 is a deubiquitinase that interacts with Cdt1, deubiquitinates it in vivo, and stabilizes it preferentially during G1/G1-S; USP37 knockdown destabilizes Cdt1 and reduces MCM loading and DNA replication fork speed. Co-immunoprecipitation; in vivo deubiquitination assay; overexpression screen; siRNA knockdown; MCM loading assay; DNA fiber assay Molecular oncology Medium 27296872
2017 3.9-Å cryo-EM structure of the yeast OCCM on DNA shows that Cdt1 has a three-domain configuration embracing Mcm2, Mcm4, and Mcm6 (nearly half the hexamer); the Cdt1 C-terminal domain contacts the Mcm6 WHD, which binds Orc4 WHD; flexible Mcm2-7 WHDs engage ORC-Cdc6; origin DNA is threaded through both rings. Cryo-EM at 3.9-Å resolution with in vitro assembled OCCM on DNA; domain mapping Nature structural & molecular biology High 28191893
2017 Cryo-EM and X-ray crystallography show that Cdt1 contains two winged-helix domains in its C-terminal half and a catalytically inactive dioxygenase-related N-terminal domain; Cdt1 interacts with Mcm2, 4, and 6, destabilizes the Mcm2-5 interface, and inhibits MCM ATPase activity; Cdt1 stabilizes MCM in a left-handed spiral with the Mcm2-5 gate open, acting as a brace for DNA entry until ORC-Cdc6 triggers ATP hydrolysis, Cdt1 ejection, and ring closure. X-ray crystallography; single-particle electron microscopy; in vitro ATPase assay; MCM loading reconstitution Nature communications High 28643783
2017 Cryo-EM of the yeast Cdt1-MCM heptamer shows that both MCM hexamer and Cdt1-MCM heptamer form left-handed coil structures with a 10–15-Å gap between Mcm5 and Mcm2; Cdt1 wraps around N-terminal regions of Mcm2, Mcm6, and Mcm4 to stabilize the open ring complex. Cryo-EM of purified yeast Cdt1-MCM complexes Nature structural & molecular biology High 28191894
2021 SLFN11 promotes CDT1 degradation in response to replicative DNA damage by binding to DDB1 of the CUL4(CDT2) E3 ubiquitin ligase at replication forks; the C-terminus and ATPase domain of SLFN11 are required for DDB1 binding and CDT1 degradation; an ATPase-dead SLFN11 mutant (E669K) found in cancer contributes to chemoresistance and retarded CDT1 degradation. Co-immunoprecipitation; siRNA knockdown; domain mutagenesis; CDT1 stability assay Proceedings of the National Academy of Sciences Medium 33536335
2023 CDT1 directly inhibits the CMG helicase at replication forks during an overlap period in early S phase when CDT1 is still present after origin firing; CDT1 suppresses CMG helicase activity, and DNA synthesis begins only after CDT1 is degraded; this separates licensing from DNA synthesis rather than strictly separating licensing from firing. Quantitative single-cell microscopy; in vitro reconstituted human DNA replication with purified CMG and CDT1; biochemical helicase assay Molecular cell High 36608667

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science (New York, N.Y.) 604 11125146
2006 A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Molecular cell 540 16949367
2001 Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin. Nature cell biology 392 11175741
2000 The Cdt1 protein is required to license DNA for replication in fission yeast. Nature 378 10766248
2006 Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. The EMBO journal 328 16482215
2004 Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage. Nature cell biology 316 15448697
2003 Radiation-mediated proteolysis of CDT1 by CUL4-ROC1 and CSN complexes constitutes a new checkpoint. Nature cell biology 256 14578910
2005 PCNA functions as a molecular platform to trigger Cdt1 destruction and prevent re-replication. Nature cell biology 255 16362051
2010 NEDD8-targeting drug MLN4924 elicits DNA rereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells. Cancer research 251 21159650
2001 The human licensing factor for DNA replication Cdt1 accumulates in G1 and is destabilized after initiation of S-phase. The Journal of biological chemistry 225 11555648
2002 Interdependent nuclear accumulation of budding yeast Cdt1 and Mcm2-7 during G1 phase. Nature cell biology 219 11836525
2003 The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation. The Journal of biological chemistry 209 12840033
2006 PCNA is a cofactor for Cdt1 degradation by CUL4/DDB1-mediated N-terminal ubiquitination. The Journal of biological chemistry 206 16407252
1994 cdt1 is an essential target of the Cdc10/Sct1 transcription factor: requirement for DNA replication and inhibition of mitosis. The EMBO journal 201 8313888
2004 Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts. Genes & development 164 15598982
2006 L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage. Cell cycle (Georgetown, Tex.) 153 16861906
2004 Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding. The Journal of biological chemistry 152 14993212
2004 Cyclin-dependent kinases phosphorylate human Cdt1 and induce its degradation. The Journal of biological chemistry 152 15004027
2008 HBO1 histone acetylase is a coactivator of the replication licensing factor Cdt1. Genes & development 147 18832067
2017 Structural basis of Mcm2-7 replicative helicase loading by ORC-Cdc6 and Cdt1. Nature structural & molecular biology 141 28191893
2006 DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint. Genes & development 141 17085480
2011 Inhibition of NEDD8-activating enzyme induces rereplication and apoptosis in human tumor cells consistent with deregulating CDT1 turnover. Cancer research 139 21487042
2013 Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA. Nature structural & molecular biology 124 23851460
2004 Structural basis for inhibition of the replication licensing factor Cdt1 by geminin. Nature 121 15286659
2004 Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis. The EMBO journal 118 15257290
2004 Cdt1 downregulation by proteolysis and geminin inhibition prevents DNA re-replication in Xenopus. The EMBO journal 117 15616577
2007 Orc6 is required for dynamic recruitment of Cdt1 during repeated Mcm2-7 loading. Genes & development 116 18006685
2002 Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity. The Journal of biological chemistry 116 12192004
2007 Nuclear accumulation of cyclin D1 during S phase inhibits Cul4-dependent Cdt1 proteolysis and triggers p53-dependent DNA rereplication. Genes & development 114 18006686
2002 Oncogenic potential of the DNA replication licensing protein CDT1. Oncogene 105 11850834
2004 Proteolysis of DNA replication licensing factor Cdt1 in S-phase is performed independently of geminin through its N-terminal region. The Journal of biological chemistry 104 15138268
2004 Cdt1 and geminin are down-regulated upon cell cycle exit and are over-expressed in cancer-derived cell lines. European journal of biochemistry 104 15291814
2006 An evolutionarily conserved function of proliferating cell nuclear antigen for Cdt1 degradation by the Cul4-Ddb1 ubiquitin ligase in response to DNA damage. The Journal of biological chemistry 99 16407242
2011 A genome-wide screen identifies p97 as an essential regulator of DNA damage-dependent CDT1 destruction. Molecular cell 97 21981919
2017 Open-ringed structure of the Cdt1-Mcm2-7 complex as a precursor of the MCM double hexamer. Nature structural & molecular biology 95 28191894
2006 Cdt1 revisited: complex and tight regulation during the cell cycle and consequences of deregulation in mammalian cells. Cell division 93 17042960
2006 Deregulation of Cdt1 induces chromosomal damage without rereplication and leads to chromosomal instability. Journal of cell science 92 16835273
2002 Geminin becomes activated as an inhibitor of Cdt1/RLF-B following nuclear import. Current biology : CB 89 11967157
2005 Degradation of Cdt1 during S phase is Skp2-independent and is required for efficient progression of mammalian cells through S phase. The Journal of biological chemistry 86 15855168
2003 The regulated association of Cdt1 with minichromosome maintenance proteins and Cdc6 in mammalian cells. The Journal of biological chemistry 86 14672932
2004 Regulation of Geminin and Cdt1 expression by E2F transcription factors. Oncogene 84 14990995
2016 Regulation and Function of Cdt1; A Key Factor in Cell Proliferation and Genome Stability. Genes 81 28025526
2011 CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation to ensure faithful DNA replication. Molecular cell 80 21981920
2012 Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore-microtubule attachment. Nature cell biology 79 22581055
2006 DDB1 maintains genome integrity through regulation of Cdt1. Molecular and cellular biology 79 16940174
2006 DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1. EMBO reports 78 17039252
2001 Expression of Cdc18/Cdc6 and Cdt1 during G2 phase induces initiation of DNA replication. The EMBO journal 77 11532929
2004 A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition. Molecular cell 76 15260975
2005 Geminin-Cdt1 balance is critical for genetic stability. Mutation research 75 15603756
2006 A Cdt1-geminin complex licenses chromatin for DNA replication and prevents rereplication during S phase in Xenopus. The EMBO journal 74 17124498
2005 Cdt1 transgenic mice develop lymphoblastic lymphoma in the absence of p53. Oncogene 72 16261166
2009 Acetylation/deacetylation modulates the stability of DNA replication licensing factor Cdt1. The Journal of biological chemistry 68 19276081
2017 Cdt1 stabilizes an open MCM ring for helicase loading. Nature communications 67 28643783
2009 Quaternary structure of the human Cdt1-Geminin complex regulates DNA replication licensing. Proceedings of the National Academy of Sciences of the United States of America 67 19906994
2021 SLFN11 promotes CDT1 degradation by CUL4 in response to replicative DNA damage, while its absence leads to synthetic lethality with ATR/CHK1 inhibitors. Proceedings of the National Academy of Sciences of the United States of America 66 33536335
2008 MCM9 binds Cdt1 and is required for the assembly of prereplication complexes. Molecular cell 65 18657502
2004 Rapid degradation of Cdt1 upon UV-induced DNA damage is mediated by SCFSkp2 complex. The Journal of biological chemistry 64 15102855
2007 Cdt1 associates dynamically with chromatin throughout G1 and recruits Geminin onto chromatin. The EMBO journal 62 17318181
2015 Initiation and termination of DNA replication during S phase in relation to cyclins D1, E and A, p21WAF1, Cdt1 and the p12 subunit of DNA polymerase δ revealed in individual cells by cytometry. Oncotarget 60 26059433
2007 Cdt1 degradation to prevent DNA re-replication: conserved and non-conserved pathways. Cell division 60 17565698
2007 Identification of novel human Cdt1-binding proteins by a proteomics approach: proteolytic regulation by APC/CCdh1. Molecular biology of the cell 59 18162579
2002 Essential role of human CDT1 in DNA replication and chromatin licensing. Journal of cell science 59 11896191
2010 Chromatin unfolding by Cdt1 regulates MCM loading via opposing functions of HBO1 and HDAC11-geminin. Cell cycle (Georgetown, Tex.) 57 20980834
2005 Functional domains of the Xenopus replication licensing factor Cdt1. Nucleic acids research 56 15653632
2002 Identification of Tah11/Sid2 as the ortholog of the replication licensing factor Cdt1 in Saccharomyces cerevisiae. Current biology : CB 55 11967159
2010 Characterization and structure determination of the Cdt1 binding domain of human minichromosome maintenance (Mcm) 6. The Journal of biological chemistry 52 20202939
2015 Cdt1-binding protein GRWD1 is a novel histone-binding protein that facilitates MCM loading through its influence on chromatin architecture. Nucleic acids research 51 25990725
2008 Cdt1 and Geminin in cancer: markers or triggers of malignant transformation? Frontiers in bioscience : a journal and virtual library 51 18508524
2006 The Caenorhabditis elegans replication licensing factor CDT-1 is targeted for degradation by the CUL-4/DDB-1 complex. Molecular and cellular biology 50 17145765
2005 Recombinant Cdt1 induces rereplication of G2 nuclei in Xenopus egg extracts. Current biology : CB 50 15668171
2014 SCF-FBXO31 E3 ligase targets DNA replication factor Cdt1 for proteolysis in the G2 phase of cell cycle to prevent re-replication. The Journal of biological chemistry 49 24828503
2011 Multiple Cdt1 molecules act at each origin to load replication-competent Mcm2-7 helicases. The EMBO journal 48 22045335
2008 Hepatitis B virus X protein increases the Cdt1-to-geminin ratio inducing DNA re-replication and polyploidy. The Journal of biological chemistry 45 18693245
2002 Regulation of CDC6, geminin, and CDT1 in human cells that undergo polyploidization. Molecular biology of the cell 45 12429841
2011 Selective ubiquitylation of p21 and Cdt1 by UBCH8 and UBE2G ubiquitin-conjugating enzymes via the CRL4Cdt2 ubiquitin ligase complex. Molecular and cellular biology 43 21628527
2011 Chromatin remodeler sucrose nonfermenting 2 homolog (SNF2H) is recruited onto DNA replication origins through interaction with Cdc10 protein-dependent transcript 1 (Cdt1) and promotes pre-replication complex formation. The Journal of biological chemistry 42 21937426
2004 Geminin has dimerization, Cdt1-binding, and destruction domains that are required for biological activity. The Journal of biological chemistry 42 15308655
2011 JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 histone acetylase and blocks replication licensing in response to stress. Molecular cell 41 21856198
2005 Expression of the licensing factors, Cdt1 and Geminin, in human colon cancer. International journal of oncology 40 16273206
2004 Cell cycle regulation of the licensing activity of Cdt1 in Xenopus laevis. Experimental cell research 40 15051497
2021 SIRT3 promotion reduces resistance to cisplatin in lung cancer by modulating the FOXO3/CDT1 axis. Cancer medicine 38 33655712
2016 USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication. Molecular oncology 37 27296872
2011 Structural insights into the Cdt1-mediated MCM2-7 chromatin loading. Nucleic acids research 37 22140117
2008 Cdt1 and Cdc6 are destabilized by rereplication-induced DNA damage. The Journal of biological chemistry 37 18617514
2007 Licensing regulators Geminin and Cdt1 identify progenitor cells of the mouse CNS in a specific phase of the cell cycle. Neuroscience 37 17533120
2011 Dynamic recruitment of licensing factor Cdt1 to sites of DNA damage. Journal of cell science 36 21224399
2011 Stress-stimulated mitogen-activated protein kinases control the stability and activity of the Cdt1 DNA replication licensing factor. Molecular and cellular biology 35 21930785
2005 Licensing for DNA replication requires a strict sequential assembly of Cdc6 and Cdt1 onto chromatin in Xenopus egg extracts. Nucleic acids research 35 15687385
2012 Regulation of cell cycle progression by forkhead transcription factor FOXO3 through its binding partner DNA replication factor Cdt1. Proceedings of the National Academy of Sciences of the United States of America 32 22451935
2007 Cdt1 and geminin: role during cell cycle progression and DNA damage in higher eukaryotes. Frontiers in bioscience : a journal and virtual library 32 17127409
2008 Human Cdt1 lacking the evolutionarily conserved region that interacts with MCM2-7 is capable of inducing re-replication. The Journal of biological chemistry 31 18184650
2007 Cdt1 interactions in the licensing process: a model for dynamic spatiotemporal control of licensing. Cell cycle (Georgetown, Tex.) 31 17598984
2013 Geminin deploys multiple mechanisms to regulate Cdt1 before cell division thus ensuring the proper execution of DNA replication. Proceedings of the National Academy of Sciences of the United States of America 30 23836640
2009 Structure of the Cdt1 C-terminal domain: conservation of the winged helix fold in replication licensing factors. Protein science : a publication of the Protein Society 30 19722278
2020 Efficient production of large deletion and gene fragment knock-in mice mediated by genome editing with Cas9-mouse Cdt1 in mouse zygotes. Methods (San Diego, Calif.) 29 32334080
2010 Proliferating cell nuclear antigen-dependent rapid recruitment of Cdt1 and CRL4Cdt2 at DNA-damaged sites after UV irradiation in HeLa cells. The Journal of biological chemistry 29 20929861
2008 Cdt1 forms a complex with the minichromosome maintenance protein (MCM) and activates its helicase activity. The Journal of biological chemistry 29 18606811
2023 CDT1 inhibits CMG helicase in early S phase to separate origin licensing from DNA synthesis. Molecular cell 27 36608667
2012 Cdt1 is differentially targeted for degradation by anticancer chemotherapeutic drugs. PloS one 26 22479651
2021 Regulation of DNA Replication Licensing and Re-Replication by Cdt1. International journal of molecular sciences 23 34068957

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