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 A licensing factor is a protein or complex of proteins that allows an origin of replication to begin DNA replication at that site. Licensing factors primarily occur in eukaryotic cells, since bacteria use simpler systems to initiate replication. Ho ...
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 A licensing factor is a protein or complex of proteins that allows an origin of replication to begin DNA replication at that site. Licensing factors primarily occur in eukaryotic cells, since bacteria use simpler systems to initiate replication. Ho ...
in the assembly of
pre-replication complex
A pre-replication complex (pre-RC) 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 ...
es (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
Cell division control protein 6 homolog is a protein that in humans is encoded by the ''CDC6'' gene.
The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc6, a protein essential for the initiation of DNA replication. ...
, 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
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 inc ...
, 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
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...
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
The African clawed frog (''Xenopus laevis''), also known as simply xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the short black ...
'' - CDT1
Interactions
DNA replication factor CDT1 has been shown to
interact with
SKP2
S-phase kinase-associated protein 2 is an enzyme that in humans is encoded by the ''SKP2'' gene.
Structure and function
Skp2 contains 424 residues in total with the ~40 amino acid F-box domain lying closer to the N-terminal region at the 94-1 ...
.
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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