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 (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.
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 SCFSKP2, 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.
CDT1 belongs to a family of replication proteins conserved from yeast to humans. Examples of orthologs in other species include:
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]
DNA replication licensing factor MCM6 is a protein that in humans is encoded by the MCM6 gene. MCM6 is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication.
Geminin, DNA replication inhibitor, also known as GMNN, is a protein in humans encoded by the GMNN gene. A nuclear protein present in most eukaryotes and highly conserved across species, numerous functions have been elucidated for geminin including roles in metazoan cell cycle, cellular proliferation, cell lineage commitment, and neural differentiation. One example of its function is the inhibition of Cdt1.
DNA replication licensing factor MCM7 is a protein that in humans is encoded by the MCM7 gene.
DNA replication licensing factor MCM2 is a protein that in humans is encoded by the MCM2 gene.
DNA replication licensing factor MCM3 is a protein that in humans is encoded by the MCM3 gene.
Cell division control protein 6 homolog is a protein that in humans is encoded by the CDC6 gene.
DNA replication licensing factor MCM4 is a protein that in humans is encoded by the MCM4 gene.
Growth arrest and DNA-damage-inducible protein GADD45 alpha is a protein that in humans is encoded by the GADD45A gene.
DNA damage-binding protein 1 is a protein that in humans is encoded by the DDB1 gene.
Origin recognition complex subunit 2 is a protein that is encoded by the ORC2 (ORC2L) gene in humans.
PITSLRE serine/threonine-protein kinase CDC2L1 is an enzyme that in humans is encoded by the CDC2L1 gene.
Cell division cycle 7-related protein kinase is an enzyme that in humans is encoded by the CDC7 gene. The Cdc7 kinase is involved in regulation of the cell cycle at the point of chromosomal DNA replication. The gene CDC7 appears to be conserved throughout eukaryotic evolution; this means that most eukaryotic cells have the Cdc7 kinase protein.
Histone cluster 2, H3, pseudogene 2, also known as HIST2H3PS2, is a human gene.
Origin recognition complex subunit 6 is a protein that in humans is encoded by the ORC6 (ORC6L) gene.
Nuclear factor 1 C-type is a protein that in humans is encoded by the NFIC gene.
Dual specificity protein phosphatase CDC14A is an enzyme that in humans is encoded by the CDC14A gene.
Mediator of RNA polymerase II transcription subunit 17 is an enzyme that in humans is encoded by the MED17 gene.
Heat shock protein 75 kDa, mitochondrial is a protein that in humans is encoded by the TRAP1 gene.
In cell biology, eukaryotes possess a regulatory system that ensures that DNA replication occurs only once per cell cycle.
DNA re-replication is an undesirable and possibly fatal occurrence in eukaryotic cells in which the genome is replicated more than once per cell cycle. Rereplication is believed to lead to genomic instability and has been implicated in the pathologies of a variety of human cancers. To prevent rereplication, eukaryotic cells have evolved multiple, overlapping mechanisms to inhibit chromosomal DNA from being partially or fully rereplicated in a given cell cycle. These control mechanisms rely on cyclin-dependent kinase (CDK) activity. DNA replication control mechanisms cooperate to prevent the relicensing of replication origins and to activate cell cycle and DNA damage checkpoints. DNA rereplication must be strictly regulated to ensure that genomic information is faithfully transmitted through successive generations.
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