CDT1 (Chromatin licensing and DNA replication factor 1) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''CDT1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
It is a
licensing factor that functions to limit DNA from replicating more than once per cell cycle.
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).
The activity of CDT1 during the
cell cycle
The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...
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.
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)
* ''
Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...
'' – 'double parked' or Dup
* ''
Xenopus laevis'' - CDT1
Interactions
DNA replication factor CDT1 has been shown to
interact with
SKP2.
Cdt1 is recruited by the
origin recognition complex
In molecular biology, origin recognition complex (ORC) is a multi-subunit DNA binding complex (6 subunits) that binds in all eukaryotes and archaea in an Adenosine triphosphate, ATP-dependent manner to origins of replication. The subunits of this ...
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.
References
Further reading
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External links
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Proteins
DNA replication
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