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FLASH GENE
Symbol CDT1 contributors: mct - updated : 23-03-2013
HGNC name chromatin licensing and DNA replication factor 1
HGNC id 24576
Corresponding disease
MGORS4 Meier-Gorlin syndrome 4
Location 16q24.3      Physical location : 88.870.185 - 88.875.665
Synonym name
  • DNA replication factor
  • double parked, Drosophila, homolog of
    • Synonym symbol(s) DUP, RIS2
    DNA
    TYPE functioning gene
    STRUCTURE 5.48 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 2742 60.4 546 - 2008 18162579
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Lymphoid/Immunethymus   highly
    Reproductivefemale systemuteruscervix predominantly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, G1, S
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a PCNA-binding motif called a PIP box
    • conjugated Other
    HOMOLOGY
    interspecies homolog to murine Cdt1 (76.3pc)
    homolog to rattus Cdt1 (74.5pc)
    Homologene
    FAMILY
  • Cdt1 family
    • CATEGORY regulatory , DNA associated , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    text replication fork
    basic FUNCTION
  • cooperating with CDC6 to promote the loading of the mini-chromosome maintenance complex onto chromatin to form the pre-replication complex necessary to initiate DNA replication
  • potential oncogene, overexpression of CDT1 promotes rereplication and generates a DNA damage response which activates the anti tumors barriers of senescence and apoptosis
  • major platform on the pre-replication complexes to integrate cell cycle signals
  • with CDC6 are destabilized by rereplication-induced DNA damage
  • is required for the formation of the pre-replicative complexes ssociating with the CDC7 kinase and recruiting CDC45 to chromatin during S phase (chromatin-bound CDT1 is first stabilized and subsequently displaced by CDC7 activity)
  • present during the G1 phase of the cell cycle
    • CELLULAR PROCESS cell cycle, checkpoint
    nucleotide, replication
    PHYSIOLOGICAL PROCESS
    text
  • DNA replication checkpoint
  • regulation of DNA replication initiation
    • PATHWAY
    metabolism
    signaling
    a component
  • part of pre-replication complex
  • CDT1-GMNN complex likely acts as a molecular switch that can enable or disable the firing of each origin of replication
    • INTERACTION
    DNA binding DNA in a sequence-, strand-, and conformation-independent manner
    RNA
    small molecule
    protein
  • GMNN
  • DDB1
  • interaction of CDT1 with ORCs is involved in the formation of the prereplicative complex, rather than in regulation of the activity of ORCs
  • DTL is a conserved component of the Cul4-DDB1 E3 that is essential to destroy CDT1 and ensure proper cell cycle regulation and timing of DNA replication
  • forming a stable complex with MCM9
  • PCNA promotes the DNA damage-induced degradation of the replication initiation factor CDT1 via the DTL E3 ubiquitin ligase complex
  • directly interacting with MYST2, coactivator of CDT1
  • DTL is a substrates of CDT1
  • KAT7 is a coactivator both for AP-1 transcription factors responding to stress-activated JNK kinases and also for the CDT1 licensing factor that ensures that DNA is replicated exactly once per cell cycle
  • unique role of FOXO3 in binding to CDT1 and maintaining its level required for cell cycle progression
  • CDT1 cooperates with the cell cycle protein CDC6 to promote loading of the minichromosome maintenance helicases (MCM) onto the chromatin-bound origin recognition complex (ORC)
  • ATR, activated after DNA damage, phosphorylates DTL and promotes the rapid degradation of CDT1 after UV irradiation in the G1 phase of the cell cycle
  • CDT1 overexpression targets GMNN to the nucleus, while reducing CDT1 levels by RNAi leads to the appearance of endogenous GMNN in the cytoplasm
  • GMNN is thought to be involved in licensing replication by promoting the accumulation of CDT1 in mitosis, because decreasing the GMNN levels prevents CDT1 accumulation and impairs DNA replication
    • cell & other
    REGULATION
    Other PCNA is a cofactor for CDT1 degradation
    CDT2 interacts with CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis
    DDB1 is involved in the regulation of CDT1 degradation
    nucleotide excision repair factors promote CDT1 destruction due to a role in recruiting PCNA to damaged DNA (
    ASSOCIATED DISORDERS
    corresponding disease(s) MGORS4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    CDT1 (and GMNN) expression is deregulated in tumor specimens and may represent novel markers useful for cancer diagnosis and prognosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS