DNA replication factor CDT1

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).{{Cite book|title=Hematology : basic principles and practice|others=Hoffman, Ronald, 1945-, Benz, Edward J., Jr.,, Silberstein, Leslie E.,, Heslop, Helen,, Weitz, Jeffrey I.,, Anastasi, John|year=2018|isbn=9780323509398|edition= Seventh|location=Philadelphia, PA|pages=Chapter 17, 176–185|oclc=1001961209|last1 = Hoffman|first1 = Ronald|last2= Benz Jr.|first2=Edward J.|last3=Silberstein|first3=Leslie E.|last4=Heslop|first4=Helen|last5=Weitz|first5=Jeffrey I.|last6=Anastasi|first6=John|last7=Salama|first7=Mohamed E.|last8=Abutalib|first8=Syed A.}}

The activity of CDT1 during the cell cycle 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.{{cite journal|vauthors=Wohlschlegel JA, Dwyer BT, Dhar SK, Cvetic C, Walter JC, Dutta A|date=December 2000|title=Inhibition of eukaryotic DNA replication by geminin binding to Cdt1|journal=Science|volume=290|issue=5500|pages=2309–12|doi=10.1126/science.290.5500.2309|pmid=11125146|bibcode=2000Sci...290.2309W}} 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:

• S. pombe – CDT1 (CDC10-dependent transcript 1){{cite journal | vauthors = Hofmann JF, Beach D | title = cdt1 is an essential target of the Cdc10/Sct1 transcription factor: requirement for DNA replication and inhibition of mitosis | journal = EMBO J. | volume = 13 | issue = 2 | pages = 425–34 |date=January 1994 | pmid = 8313888 | pmc = 394824 | doi = 10.1002/j.1460-2075.1994.tb06277.x }}
• Drosophila melanogaster – 'double parked' or Dup{{cite journal | vauthors = Nakajima H, Watanabe N, Shibata F, Kitamura T, Ikeda Y, Handa M | title = N-terminal region of CCAAT/enhancer-binding protein epsilon is critical for cell cycle arrest, apoptosis, and functional maturation during myeloid differentiation | journal = J. Biol. Chem. | volume = 281 | issue = 20 | pages = 14494–502 |date=May 2006 | pmid = 16531405 | doi = 10.1074/jbc.M600575200 | doi-access = free }}
• Xenopus laevis - CDT1{{cite journal | vauthors = Maiorano D, Moreau J, Méchali M | title = XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis. | journal = Nature | volume = 404 | pages = 622–5 |date=April 2000 | pmid = 10766247 | issue = 6778 | doi = 10.1038/35007104 | bibcode = 2000Natur.404..622M | s2cid = 4416138 }}

DNA replication factor CDT1 has been shown to interact with SKP2.{{cite journal | vauthors = Li X, Zhao Q, Liao R, Sun P, Wu X | title = The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation | journal = J. Biol. Chem. | volume = 278 | issue = 33 | pages = 30854–8 | year = 2003 | pmid = 12840033 | doi = 10.1074/jbc.C300251200 | doi-access = free }} 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.{{cite journal | vauthors = Machida YJ, Dutta A | title = Cellular checkpoint mechanisms monitoring proper initiation of DNA replication | journal = J. Biol. Chem. | volume = 280 | issue = 8 | pages = 6253–6 | year = 2005 | pmid = 15591064 | doi = 10.1074/jbc.R400037200 | doi-access = free }}

{{Reflist}}

{{refbegin | 2}}

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{{refend}}

• {{PDBe-KB2|Q9H211|Human DNA replication factor Cdt1}}
• {{PDBe-KB2|Q8R4E9|Mouse DNA replication factor Cdt1}}

{{DNA replication}}

Category:Proteins

Category:DNA replication

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