CDT1 (chromatin licensing and DNA replication factor 1)

2009-11-01   Rekha Deka , Ranjan Tamuli 

Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati-781 039, Assam, India




Atlas Image


DNA size 5.48 kb; mRNA size 2674 bp; 10 exons.


Atlas Image


546 amino acids; 60433 Da.
CDT1 contains cyclin binding motif 68-70 (3), and region for geminin interaction 150-190 (41). Cyclin-binding motif is the target for phosphorylation by cyclin A-dependent kinases, which results in the binding of Cdt1 to the F-box protein Skp2 and subsequent degradation. Interaction with geminin, a small regulatory protein active during S, G2, and M phases of the cell cycle, protects CDT1 from ubiquitin mediated degradation. Six natural variants, A135V (VAR-029163), R172C (VAR-029164), R234C (VAR-054504), T262A (VAR-054505), E456A (VAR-029165), and A537V (VAR-024408) have been reported.
Isoforms : There are three different isoforms, aApr07 (complete), bApr07 (partial), and cApr07 (COOH complete); all three isoforms putatively encode good proteins.
Post translational modifications : Phosphorylation occurs at position Thr29, Ser31, Ser318, Ser372, and Ser394; however, phosphorylation does not affect binding to geminin.


Widely expressed, highly expressed in liver, thymus, and predominantly expressed in uterus and cervix of female reproductive system.




The CDT1 protein is required for the formation of the pre-replicative complexes. CDT1 cooperates with CDC6 to promote loading of the mini-chromosome maintenance complex (MCM2-7) onto chromatin to form pre-replication complex necessary for the initiation of DNA replication. Moreover, CDT1 associates with the CDC7 kinase and recruits CDC45 to chromatin during S phase. Chromatin-bound CDT1 is first stabilized and subsequently displaced by CDC7 activity, which ensures timely execution of DNA replication. CDT1 is also a potential oncogene; overexpression of CDT1 promotes rereplication and generates a DNA damage senescence and response that activates the antitumor barriers of senescence and apoptosis.
Regulation : CDT1 is regulated either by cell cycle dependent proteolysis during S and G2 phase or by geminin. Proteolysis of CDT1 during S and G2 phases is dependent on the CDK2 -cyclin A mediated phosphorylation of CDT1 and subsequent proteolysis by SCF-Skp2 complex. CDT1 activity is also inhibited by the tight binding of geminin that blocks the ability of CDT1 to load MCM2-7 onto DNA.


The percent identity below represents identity of CDT1 over an aligned region in UniGene.
-Mus musculus : 82 % (percent identity)
-Bos taurus : 76.2 %
-Canis familiaris : 74.54 %
-Rattus norvegicus : 74.49 %
-Xenopus laevis : 62.5 %
-Danio rerio : 60 %.



The RRL --->AAA mutation in the cyclin binding motif abolishes the binding of Cyclin A-dependent protein kinases with CDT1.

Implicated in

Entity name
Lung carcinoma
In a subset of non-small-cell lung carcinomas (NSCLCs), CDT1 is significantly overexpressed that is positively correlated with CDC6 levels. Overexpression of CDT1-CDC6 in concert with p53-mutation is associated with higher tumor growth values and frequent aneuploidy compared with tumor bearing intact p53. These suggest a synergistic effect between CDT1-CDC6 overexpression and mutant-p53 over tumor growth and chromosomal instability in non-small-cell lung carcinomas.
Entity name
Colon cancer
CDT1 is highly expressed in human neoplastics lesions of the colon; however, its cell cycle phase specific expression profile appears to be preserved during human carcinogenesis. Overexpression of CDT1 results in rereplication, a form of endogenous DNA damage.
Entity name
Chromosomal damage
Overexpression of CDT1 induces chromosomal damage and activation of ATM-Chk2 without rereplication, resulting in chromosomal instability in normal human foreskin fibroblasts (HFF2) immortalized by telomerase. Deregulated CDT1 overexpression causes chronic chromosomal damage and instability that can eventually results in carcinogenesis. CDT1 is also highly expressed in cancer cells CaSki, HeLa, LNcap, MCF7, MDAMB231, and Saos. Overexpression of CDT1 may be at least partly due to increased transcription or increased gene copy number and CDT1 protein levels are much less affected by contact inhibition.


Pubmed IDLast YearTitleAuthors
190547652009Human CDT1 associates with CDC7 and recruits CDC45 to chromatin during S phase.Ballabeni A et al
162732062005Expression of the licensing factors, Cdt1 and Geminin, in human colon cancer.Bravou V et al
146729322004The regulated association of Cdt1 with minichromosome maintenance proteins and Cdc6 in mammalian cells.Cook JG et al
18657501991Low pH medium induces calcium dependent release of CGRP from sensory nerves of guinea-pig dural venous sinuses.Fanciullacci M et al
186175142008Cdt1 and Cdc6 are destabilized by rereplication-induced DNA damage.Hall JR et al
164072422006An evolutionarily conserved function of proliferating cell nuclear antigen for Cdt1 degradation by the Cul4-Ddb1 ubiquitin ligase in response to DNA damage.Hu J et al
154663992004Overexpression of the replication licensing regulators hCdt1 and hCdc6 characterizes a subset of non-small-cell lung carcinomas: synergistic effect with mutant p53 on tumor growth and chromosomal instability--evidence of E2F-1 transcriptional control over hCdt1.Karakaidos P et al
180068352007Deregulated overexpression of hCdt1 and hCdc6 promotes malignant behavior.Liontos M et al
149932122004Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding.Sugimoto N et al
158551682005Degradation of Cdt1 during S phase is Skp2-independent and is required for efficient progression of mammalian cells through S phase.Takeda DY et al
168352732006Deregulation of Cdt1 induces chromosomal damage without rereplication and leads to chromosomal instability.Tatsumi Y et al
152918142004Cdt1 and geminin are down-regulated upon cell cycle exit and are over-expressed in cancer-derived cell lines.Xouri G et al
147122112004The destruction box of human Geminin is critical for proliferation and tumor growth in human colon cancer cells.Yoshida K et al

Other Information

Locus ID:

NCBI: 81620
MIM: 605525
HGNC: 24576
Ensembl: ENSG00000167513


dbSNP: 81620
ClinVar: 81620
TCGA: ENSG00000167513


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
Mitotic G1-G1/S phasesREACTOMER-HSA-453279
G1/S TransitionREACTOMER-HSA-69206
G1/S-Specific TranscriptionREACTOMER-HSA-69205
Activation of the pre-replicative complexREACTOMER-HSA-68962
E2F mediated regulation of DNA replicationREACTOMER-HSA-113510
Synthesis of DNAREACTOMER-HSA-69239
Switching of origins to a post-replicative stateREACTOMER-HSA-69052
Orc1 removal from chromatinREACTOMER-HSA-68949
Regulation of DNA replicationREACTOMER-HSA-69304
Association of licensing factors with the pre-replicative complexREACTOMER-HSA-69298
Removal of licensing factors from originsREACTOMER-HSA-69300
M/G1 TransitionREACTOMER-HSA-68874
DNA Replication Pre-InitiationREACTOMER-HSA-69002
Assembly of the pre-replicative complexREACTOMER-HSA-68867
CDT1 association with the CDC6:ORC:origin complexREACTOMER-HSA-68827
DNA ReplicationREACTOMER-HSA-69306

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
169493672006A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1.300
128400332003The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation.102
168619062006L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage.97
170854802006DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint.80
180068352007Deregulated overexpression of hCdt1 and hCdc6 promotes malignant behavior.78
150040272004Cyclin-dependent kinases phosphorylate human Cdt1 and induce its degradation.76
152572902004Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis.71
149932122004Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding.70
164072422006An evolutionarily conserved function of proliferating cell nuclear antigen for Cdt1 degradation by the Cul4-Ddb1 ubiquitin ligase in response to DNA damage.64
188320672008HBO1 histone acetylase is a coactivator of the replication licensing factor Cdt1.62


Rekha Deka ; Ranjan Tamuli

CDT1 (chromatin licensing and DNA replication factor 1)

Atlas Genet Cytogenet Oncol Haematol. 2009-11-01

Online version: