DNA replication factor CDT1
Encyclopedia
DNA replication factor Cdt1 is a protein
that in humans is encoded by the CDT1 gene
.
The protein encoded by this gene is a key licensing factor which, along with the protein Cdc6
, functions to license DNA by forming the pre-replication complex
(pre-RC). Its activity during the cell cycle
is tightly regulated by its association with the protein geminin
, which both inhibits Cdt1 activity during S phase in order to prevent re-replication of DNA and prevents it from ubiquitination and subsequent proteolysis.
with SKP2
. 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. (ref Machida and Dutta, cellylar checkpoint mechanisms monitoring proper initiation of DNA replication, the journal of biological chemistry, 2005, vol 280 number 8)
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the CDT1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
The protein encoded by this gene is a key licensing factor which, along with the protein Cdc6
Cdc6
Cdc6, or Cell Division Cycle 6, is a protein in eukaryotic cells that is studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate...
, functions to license DNA by forming the pre-replication complex
Pre-replication complex
A pre-replication complex is a protein complex that forms at the origin of replication during the initiation step of DNA replication. Formation of the pre-RC is required for DNA replication to occur. Complete and faithful replication of the genome ensures that each daughter cell will carry the...
(pre-RC). Its activity during the cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
is tightly regulated by its association with the protein geminin
Geminin
Geminin, DNA replication inhibitor, also known as GMNN, is a protein in humans encoded by the GMNN gene.Geminin is a nuclear protein that is present in most eukaryotics and highly conserved across species...
, which both inhibits Cdt1 activity during S phase in order to prevent re-replication of DNA and prevents it from ubiquitination and subsequent proteolysis.
Orthologs
CDT1 belongs to a family of replication proteins conserved from yeast to humans. Examples of orthlogs in other species include:- S. pombeSchizosaccharomyces pombeSchizosaccharomyces pombe, also called "fission yeast", is a species of yeast. It is used as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measure 3 to 4 micrometres in diameter and 7 to 14 micrometres in length...
– cdt1 (cdc10-dependent transcript 1) - Drosophila melanogasterDrosophila melanogasterDrosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
– 'double parked' or Dup - Xenopus laevisAfrican clawed frogThe African clawed frog is a species of South African aquatic frog of the genus Xenopus. Its name is derived from the three short claws on each hind foot, which it uses to tear apart its food...
- Cdt1
Interactions
DNA replication factor CDT1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with SKP2
SKP2
S-phase kinase-associated protein 2 is an enzyme that in humans is encoded by the SKP2 gene.- Function :This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box domain...
. Cdt1 is recruited by the origin recognition complex
Origin Recognition Complex
ORC or Origin Recognition Complex is a multi-subunit DNA binding complex that binds in all eukaryotes in an ATP-dependent manner to origins of replication....
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. (ref Machida and Dutta, cellylar checkpoint mechanisms monitoring proper initiation of DNA replication, the journal of biological chemistry, 2005, vol 280 number 8)