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{{Infobox_gene}}
{{Infobox_gene}}
'''DNA replication factor Cdt1''' is a [[protein]] that in humans is encoded by the ''CDT1'' [[gene]].<ref name="pmid11896191">{{cite journal | vauthors = Rialland M, Sola F, Santocanale C | title = Essential role of human CDT1 in DNA replication and chromatin licensing | journal = J Cell Sci | volume = 115 | issue = Pt 7 | pages = 1435–40 |date=March 2002 | pmid = 11896191 | pmc =  | doi =  }}</ref><ref name="pmid11555648">{{cite journal | vauthors = Nishitani H, Taraviras S, Lygerou Z, Nishimoto T | title = The human licensing factor for DNA replication Cdt1 accumulates in G1 and is destabilized after initiation of S-phase | journal = J Biol Chem | volume = 276 | issue = 48 | pages = 44905–11 |date=November 2001 | pmid = 11555648 | pmc =  | doi = 10.1074/jbc.M105406200 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CDT1 chromatin licensing and DNA replication factor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=81620| accessdate = }}</ref>
'''CDT1''' (Chromatin licensing and DNA replication factor 1) is a [[protein]] that in humans is encoded by the ''CDT1'' [[gene]].<ref name="pmid11896191">{{cite journal | vauthors = Rialland M, Sola F, Santocanale C | title = Essential role of human CDT1 in DNA replication and chromatin licensing | journal = J Cell Sci | volume = 115 | issue = Pt 7 | pages = 1435–40 |date=March 2002 | pmid = 11896191 | pmc =  | doi =  }}</ref><ref name="pmid11555648">{{cite journal | vauthors = Nishitani H, Taraviras S, Lygerou Z, Nishimoto T | title = The human licensing factor for DNA replication Cdt1 accumulates in G1 and is destabilized after initiation of S-phase | journal = J Biol Chem | volume = 276 | issue = 48 | pages = 44905–11 |date=November 2001 | pmid = 11555648 | pmc =  | doi = 10.1074/jbc.M105406200 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CDT1 chromatin licensing and DNA replication factor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=81620| accessdate = }}</ref><ref>{{Cite web|url=https://ghr.nlm.nih.gov/gene/CDT1|title=CDT1 gene|last=Reference|first=Genetics Home|website=Genetics Home Reference|language=en|access-date=2018-07-19}}</ref> It is a licensing factor that functions to limit DNA from replicating more than once per cell cycle.


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.<ref name="pmid11125146">{{cite journal | vauthors = Wohlschlegel JA, Dwyer BT, Dhar SK, Cvetic C, Walter JC, Dutta A | title = Inhibition of eukaryotic DNA replication by geminin binding to Cdt1 | journal = Science | volume = 290 | issue = 5500 | pages = 2309–12 |date=December 2000 | pmid = 11125146 | doi = 10.1126/science.290.5500.2309 | url = }}</ref>
== Role in pre-replication complexes ==
The protein encoded by this gene is a key [[licensing factor]] in the assembly of [[pre-replication complex]]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|CDC6]], are then recruited to the forming pre-RC, followed by minichromosome maintenance complexes (MCM2-7).<ref>{{Cite book|url=https://www.worldcat.org/oclc/1001961209|title=Hematology : basic principles and practice|last=|first=|publisher=|others=Hoffman, Ronald, 1945-, Benz, Edward J., Jr.,, Silberstein, Leslie E.,, Heslop, Helen,, Weitz, Jeffrey I.,, Anastasi, John,|year=|isbn=9780323509398|edition= Seventh|location=Philadelphia, PA|pages=Chapter 17, 176–185|oclc=1001961209}}</ref>
 
The activity of CDT1 during the [[cell cycle]] is tightly regulated during the S phase by the protein [[geminin]], which inhibits its, and by SCF<sup>SKP2</sup>, which ubiquinates the protein to tag it for proteasomal degradation.<ref name="pmid11125146">{{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|url=|journal=Science|volume=290|issue=5500|pages=2309–12|doi=10.1126/science.290.5500.2309|pmid=11125146}}</ref> This regulation is important in preventing relicensing, thus ensuring that DNA is only replicated once per cell cycle.


==Orthologs==
==Orthologs==
CDT1 belongs to a family of replication proteins conserved from yeast to humans. Examples of [[homology (biology)#Orthology|orthologs]] in other species include:
CDT1 belongs to a family of replication proteins conserved from yeast to humans. Examples of [[homology (biology)#Orthology|orthologs]] in other species include:
* ''[[Schizosaccharomyces pombe|S. pombe]]'' – cdt1 (cdc10-dependent transcript 1)<ref name="pmid8313888">{{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 | url = | issn = }}</ref>
* ''[[Schizosaccharomyces pombe|S. pombe]]'' – CDT1 (CDC10-dependent transcript 1)<ref name="pmid8313888">{{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 | url = | issn = }}</ref>
* ''[[Drosophila melanogaster]]'' – 'double parked' or Dup<ref name="pmid16531405">{{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 | url =  }}</ref>
* ''[[Drosophila melanogaster]]'' – 'double parked' or Dup<ref name="pmid16531405">{{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 | url =  }}</ref>
* ''[[African clawed frog|Xenopus laevis]]'' - Cdt1<ref name="pmid10766247">{{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 | url = | issue = 6778 | doi = 10.1038/35007104 }}</ref>
* ''[[African clawed frog|Xenopus laevis]]'' - CDT1<ref name="pmid10766247">{{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 | url = | issue = 6778 | doi = 10.1038/35007104 }}</ref>


== Interactions ==
== Interactions ==
DNA replication factor CDT1 has been shown to [[Protein-protein interaction|interact]] with [[SKP2]].<ref name="pmid12840033">{{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 }}</ref> 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 name="pmid15591064">{{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 }}</ref>
DNA replication factor CDT1 has been shown to [[Protein-protein interaction|interact]] with [[SKP2]].<ref name="pmid12840033">{{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 }}</ref> 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 name="pmid15591064">{{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 }}</ref>


==References==
==References==
{{Reflist|2}}
{{Reflist}}


==Further reading==
==Further reading==

Revision as of 04:43, 27 July 2018

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CDT1 (Chromatin licensing and DNA replication factor 1) is a protein that in humans is encoded by the CDT1 gene.[1][2][3][4] 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).[5]

The activity of CDT1 during the cell cycle is tightly regulated during the S phase by the protein geminin, which inhibits its, and by SCFSKP2, which ubiquinates the protein to tag it for proteasomal degradation.[6] 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:

Interactions

DNA replication factor CDT1 has been shown to interact with SKP2.[10] 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.[11]

References

  1. ↑ Rialland M, Sola F, Santocanale C (March 2002). "Essential role of human CDT1 in DNA replication and chromatin licensing". J Cell Sci. 115 (Pt 7): 1435–40. PMID 11896191.
  2. ↑ Nishitani H, Taraviras S, Lygerou Z, Nishimoto T (November 2001). "The human licensing factor for DNA replication Cdt1 accumulates in G1 and is destabilized after initiation of S-phase". J Biol Chem. 276 (48): 44905–11. doi:10.1074/jbc.M105406200. PMID 11555648.
  3. ↑ "Entrez Gene: CDT1 chromatin licensing and DNA replication factor 1".
  4. ↑ Reference, Genetics Home. "CDT1 gene". Genetics Home Reference. Retrieved 2018-07-19.
  5. ↑ Hematology : basic principles and practice. Hoffman, Ronald, 1945-, Benz, Edward J., Jr.,, Silberstein, Leslie E.,, Heslop, Helen,, Weitz, Jeffrey I.,, Anastasi, John, (Seventh ed.). Philadelphia, PA. pp. Chapter 17, 176–185. ISBN 9780323509398. OCLC 1001961209.
  6. ↑ Wohlschlegel JA, Dwyer BT, Dhar SK, Cvetic C, Walter JC, Dutta A (December 2000). "Inhibition of eukaryotic DNA replication by geminin binding to Cdt1". Science. 290 (5500): 2309–12. doi:10.1126/science.290.5500.2309. PMID 11125146.
  7. ↑ Hofmann JF, Beach D (January 1994). "cdt1 is an essential target of the Cdc10/Sct1 transcription factor: requirement for DNA replication and inhibition of mitosis". EMBO J. 13 (2): 425–34. PMC 394824. PMID 8313888.
  8. ↑ Nakajima H, Watanabe N, Shibata F, Kitamura T, Ikeda Y, Handa M (May 2006). "N-terminal region of CCAAT/enhancer-binding protein epsilon is critical for cell cycle arrest, apoptosis, and functional maturation during myeloid differentiation". J. Biol. Chem. 281 (20): 14494–502. doi:10.1074/jbc.M600575200. PMID 16531405.
  9. ↑ Maiorano D, Moreau J, Méchali M (April 2000). "XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis". Nature. 404 (6778): 622–5. doi:10.1038/35007104. PMID 10766247.
  10. ↑ Li X, Zhao Q, Liao R, Sun P, Wu X (2003). "The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation". J. Biol. Chem. 278 (33): 30854–8. doi:10.1074/jbc.C300251200. PMID 12840033.
  11. ↑ Machida YJ, Dutta A (2005). "Cellular checkpoint mechanisms monitoring proper initiation of DNA replication". J. Biol. Chem. 280 (8): 6253–6. doi:10.1074/jbc.R400037200. PMID 15591064.

Further reading


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