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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''CDT1''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
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 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. ...
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 series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and sub ...
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
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 sp ...
in other species include:
* ''
S. pombe
''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measur ...
'' – CDT1 (CDC10-dependent transcript 1)
* ''
Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (the taxonomic 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" or "pomace fly". Starting with ...
'' – 'double parked' or Dup
* ''
Xenopus laevis
The African clawed frog (''Xenopus laevis'', also known as the 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 three short claws o ...
'' - CDT1
Interactions
DNA replication factor CDT1 has been shown to
interact
Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex trai ...
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
Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by the ''CHEK1'' gene. Chk1 coordinates the DNA damage response (DDR) and cell cycle checkpoint response. Activation of Chk ...
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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