DNA replication factor CDT1

CDT1 (Chromatin licensing and DNA replication factor 1) is a protein that in humans is encoded by the CDT1 gene.^[5][6][7][8] It is a licensing factor that functions to limit DNA from replicating more than once per cell cycle.

CDT1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LE8, 2WVR
Identifiers
Aliases	CDT1, DUP, RIS2, chromatin licensing and DNA replication factor 1
External IDs	OMIM: 605525; MGI: 1914427; HomoloGene: 32650; GeneCards: CDT1; OMA:CDT1 - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q24.3 Start 88,803,789 bp[1] End 88,809,258 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 E1 Start 123,294,754 bp[2] End 123,300,293 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of paranasal sinus oocyte gingival epithelium secondary oocyte ventricular zone ganglionic eminence mucosa of transverse colon gonad trabecular bone bone marrow Top expressed in fetal liver hematopoietic progenitor cell endocardial cushion tibiofemoral joint abdominal wall primitive streak condyle fossa Paneth cell vas deferens primary oocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding protein binding chromatin binding DNA polymerase binding Cellular component cytosol nucleus nucleoplasm nuclear body chromosome, centromeric region chromosome kinetochore cytoplasm Biological process DNA replication checkpoint signaling DNA replication cell cycle regulation of nuclear cell cycle DNA replication regulation of transcription involved in G1/S transition of mitotic cell cycle regulation of DNA-dependent DNA replication initiation chromosome segregation attachment of mitotic spindle microtubules to kinetochore mitotic cell cycle positive regulation of protein-containing complex assembly regulation of chromosome organization positive regulation of chromatin binding cell division kinetochore organization DNA replication preinitiation complex assembly response to sorbitol deactivation of mitotic spindle assembly checkpoint regulation of DNA replication origin binding negative regulation of protein localization to kinetochore positive regulation of protein localization to kinetochore positive regulation of DNA-dependent DNA replication positive regulation of mediator complex assembly G1/S transition of mitotic cell cycle positive regulation of DNA replication mitotic cytokinesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 81620 67177 Ensembl ENSG00000167513 ENSMUSG00000006585 UniProt Q9H211 Q8R4E9 RefSeq (mRNA) NM_030928 NM_026014 RefSeq (protein) NP_112190 NP_080290 Location (UCSC) Chr 16: 88.8 – 88.81 Mb Chr 8: 123.29 – 123.3 Mb PubMed search [3] [4]
Wikidata
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Role in pre-replication complexes

The protein encoded by this gene is a key licensing factor in the assembly of pre-replication complexes (pre-RC), which occurs during the G1 phase of the cell cycle. In the assembly of pre-RCs, origin recognition complexes (ORC1-6) recognize and bind to DNA replication origins. CDT1, along with the protein CDC6, are then recruited to the forming pre-RC, followed by minichromosome maintenance complexes (MCM2-7).^[9]

The activity of CDT1 during the cell cycle is tightly regulated during the S phase by the protein geminin, which inhibits it, and by SCF^SKP2, which ubiquinates the protein to tag it for proteasomal degradation.^[10] This regulation is important in preventing relicensing, thus ensuring that DNA is only replicated once per cell cycle.

Orthologs

CDT1 belongs to a family of replication proteins conserved from yeast to humans. Examples of orthologs in other species include:

• S. pombe – CDT1 (CDC10-dependent transcript 1)^[11]
• Drosophila melanogaster – 'double parked' or Dup^[12]
• Xenopus laevis - CDT1^[13]

Interactions

DNA replication factor CDT1 has been shown to interact with SKP2.^[14] Cdt1 is recruited by the origin recognition complex in origin licensing. Null-mutations for CDT1 are lethal in yeast; the spores undergo mitosis without DNA replication. The overexpression of CDT1 causes rereplication in H. sapiens, which activates the Chk1 pathway, preventing entry into mitosis.^[15]