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.
Eukaryotic DNA replication is a conserved mechanism that restricts DNA replication to once per cell cycle. Eukaryotic DNA replication of chromosomal DNA is central for the duplication of a cell and is necessary for the maintenance of the eukaryotic genome.
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.
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DNA replication licensing factor MCM4 is a protein that in humans is encoded by the MCM4 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.
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.
Cyclin-dependent kinases regulatory subunit 1 is a protein that in humans is encoded by the CKS1B 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.
Mediator of RNA polymerase II transcription subunit 17 is an enzyme that in humans is encoded by the MED17 gene.
In cell biology, eukaryotes possess a regulatory system that ensures that DNA replication occurs only once per cell cycle.
Origin recognition complex subunit 1 is a protein that in humans is encoded by the ORC1 gene. It is closely related to CDC6, and both are the same protein in archaea.
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.
Zoi Lygerou is a Greek molecular biologist and associate professor at Patras Medical School. Lygerou's works have been published in such journals as the European Journal of Biochemistry, Journal of Cell Science, the Molecular and Cellular Biology journal, Journal of Biological Chemistry, and both Science and Nature journals among others. She is especially known for her work on cell cycle control mechanisms in eukaryotic organisms, and has done research at the University of Patras since 1999. Lygerou has also held positions at the European Molecular Biology Laboratory (EMBL) and at the Imperial Cancer Research Fund in London under Paul Nurse.
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