CDT1: Chromatin Licensing and DNA Replication Factor 1
A key regulator of DNA replication initiation and genome stability
Gene Information Card
| Symbol | CDT1 |
|---|---|
| Full Name | Chromatin Licensing and DNA Replication Factor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q24.3 |
| NCBI Gene ID | 81620 ncbi.nlm.nih.gov/gene/81620 |
| Ensembl ID | ENSG00000167513 |
| UniProt ID | Q9H211 |
| OMIM ID | 605525 |
| HGNC ID | 24576 |
| Aliases | DUP, RIS2, MGS5 |
Description
CDT1 encodes a protein essential for the licensing of DNA replication origins during the G1 phase of the cell cycle. It forms a complex with the origin recognition complex (ORC) and CDC6 to load the minichromosome maintenance (MCM) complex onto chromatin, a critical step for replication initiation. CDT1 activity is tightly regulated by geminin and ubiquitin-mediated degradation to prevent re-replication and maintain genome stability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Meier-Gorlin syndrome 5 (MGS5) | Loss-of-function mutations in CDT1 impair pre-replication complex assembly, leading to reduced cell proliferation and primordial dwarfism | OMIM #613804 |
| Colorectal cancer | Overexpression of CDT1 leads to replication stress and genomic instability, promoting tumorigenesis | COSMIC; PMID: 20818439 |
| Breast cancer | Elevated CDT1 levels correlate with poor prognosis and increased DNA damage response activation | COSMIC; PMID: 25652263 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 18.2 | High |
| Bone marrow | 12.5 | Medium |
| Lymph node | 10.8 | Medium |
| Brain | 3.1 | Low |
| Liver | 2.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.4 | Cervical cancer cell line |
| HEK293 | 12.1 | Embryonic kidney cell line |
| HCT116 | 14.7 | Colorectal carcinoma cell line |
| MCF7 | 11.3 | Breast cancer cell line |
| K562 | 9.8 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.457C>T (p.Arg153*) | Nonsense | <0.01% | Loss of function; associated with Meier-Gorlin syndrome |
| c.800G>A (p.Arg267Gln) | Missense | <0.01% | Impaired MCM loading; MGS5 |
| c.1A>G (p.Met1?) | Start loss | <0.01% | Loss of function; MGS5 |
| Amplification | Copy number gain | ~5% in breast cancer | Overexpression; oncogenic potential |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and start-loss mutations in CDT1 impair licensing activity, causing Meier-Gorlin syndrome 5.
Gain of Function (GOF)
Amplification and overexpression of CDT1 in cancers lead to re-replication and genomic instability.
Dominant Negative (DN)
Not reported for CDT1.
View complete mutation data：
Gene Ontology (GO)
| • DNA replication initiation | • DNA replication preinitiation complex assembly |
| • chromatin binding | • protein heterodimerization activity |
| • MCM complex loading | • cell cycle G1/S phase transition |
Pathways
• Cell Cycle (KEGG: hsa04110)
• DNA replication (KEGG: hsa03030)
• CDT1 association with the CDC6:ORC:origin complex (Reactome: R-HSA-68874)
Protein Summary
CDT1 is a 546-amino acid protein (UniProt Q9H211) that localizes to the nucleus and is essential for the formation of the pre-replication complex. It directly interacts with the MCM complex and is inhibited by geminin during S, G2, and M phases to prevent re-replication. Post-translational regulation includes ubiquitination by CUL4-DDB1 and subsequent proteasomal degradation. Structural studies reveal a winged-helix domain critical for MCM loading.
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