View source for DNA replication factor CDT1

{{Short description|Protein found in humans}}
{{Infobox_gene}}
'''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 | doi = 10.1242/jcs.115.7.1435 | pmid = 11896191 }}</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 | doi = 10.1074/jbc.M105406200 | doi-access = free }}</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}}</ref><ref>{{Cite web|url=https://ghr.nlm.nih.gov/gene/CDT1|title=CDT1 gene|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.

== 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|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.}}</ref>

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<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|journal=Science|volume=290|issue=5500|pages=2309–12|doi=10.1126/science.290.5500.2309|pmid=11125146|bibcode=2000Sci...290.2309W}}</ref> 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 [[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 | doi = 10.1002/j.1460-2075.1994.tb06277.x }}</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 | doi-access = free }}</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 | issue = 6778 | doi = 10.1038/35007104 | bibcode = 2000Natur.404..622M | s2cid = 4416138 }}</ref>

== 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 | doi-access = free }}</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 [[CHEK1|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 | doi-access = free }}</ref>

==References==
{{Reflist}}

==Further reading==
{{refbegin | 2}}
*{{cite journal  | vauthors=Xouri G, Dimaki M, Bastiaens PI, Lygerou Z |title=Cdt1 interactions in the licensing process: a model for dynamic spatiotemporal control of licensing. |journal=Cell Cycle |volume=6 |issue= 13 |pages= 1549–52 |year= 2007 |pmid= 17598984 |doi=10.4161/cc.6.13.4455  |doi-access=free }}
*{{cite journal  | vauthors=Andersson B, Wentland MA, Ricafrente JY |title=A "double adaptor" method for improved shotgun library construction. |journal=Anal. Biochem. |volume=236 |issue= 1 |pages= 107–13 |year= 1996 |pmid= 8619474 |doi= 10.1006/abio.1996.0138 |display-authors=etal}}
*{{cite journal  | vauthors=Yu W, Andersson B, Worley KC |title=Large-scale concatenation cDNA sequencing. |journal=Genome Res. |volume=7 |issue= 4 |pages= 353–8 |year= 1997 |pmid= 9110174 |doi=  10.1101/gr.7.4.353| pmc=139146  |display-authors=etal}}
*{{cite journal  | vauthors=Nishitani H, Lygerou Z, Nishimoto T, Nurse P |title=The Cdt1 protein is required to license DNA for replication in fission yeast. |journal=Nature |volume=404 |issue= 6778 |pages= 625–8 |year= 2000 |pmid= 10766248 |doi= 10.1038/35007110 |bibcode=2000Natur.404..625N |s2cid=205005540 }}
*{{cite journal  | vauthors=Whittaker AJ, Royzman I, Orr-Weaver TL |title=Drosophila double parked: a conserved, essential replication protein that colocalizes with the origin recognition complex and links DNA replication with mitosis and the down-regulation of S phase transcripts. |journal=Genes Dev. |volume=14 |issue= 14 |pages= 1765–76 |year= 2000 |doi=10.1101/gad.14.14.1765 |pmid= 10898791 | pmc=316778  }}
*{{cite journal  | vauthors=Wohlschlegel JA, Dwyer BT, Dhar SK |title=Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. |journal=Science |volume=290 |issue= 5500 |pages= 2309–12 |year= 2001 |pmid= 11125146 |doi= 10.1126/science.290.5500.2309 |bibcode=2000Sci...290.2309W |display-authors=etal}}
*{{cite journal  | vauthors=Yanagi K, Mizuno T, You Z, Hanaoka F |title=Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity. |journal=J. Biol. Chem. |volume=277 |issue= 43 |pages= 40871–80 |year= 2002 |pmid= 12192004 |doi= 10.1074/jbc.M206202200 |doi-access= free }}
*{{cite journal  | vauthors=Bermejo R, Vilaboa N, Calés C |title=Regulation of CDC6, geminin, and CDT1 in human cells that undergo polyploidization. |journal=Mol. Biol. Cell |volume=13 |issue= 11 |pages= 3989–4000 |year= 2003 |pmid= 12429841 |doi= 10.1091/mbc.E02-04-0217  | pmc=133609 }}
*{{cite journal  | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 |bibcode=2002PNAS...9916899M |display-authors=etal|doi-access=free }}
*{{cite journal  | vauthors=Li X, Zhao Q, Liao R |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 |display-authors=etal|doi-access=free }}
*{{cite journal  | vauthors=Cook JG, Chasse DA, Nevins JR |title=The regulated association of Cdt1 with minichromosome maintenance proteins and Cdc6 in mammalian cells. |journal=J. Biol. Chem. |volume=279 |issue= 10 |pages= 9625–33 |year= 2004 |pmid= 14672932 |doi= 10.1074/jbc.M311933200 |doi-access= free }}
*{{cite journal  | vauthors=Sugimoto N, Tatsumi Y, Tsurumi T |title=Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding. |journal=J. Biol. Chem. |volume=279 |issue= 19 |pages= 19691–7 |year= 2004 |pmid= 14993212 |doi= 10.1074/jbc.M313175200 |display-authors=etal|doi-access=free }}
*{{cite journal  | vauthors=Liu E, Li X, Yan F |title=Cyclin-dependent kinases phosphorylate human Cdt1 and induce its degradation. |journal=J. Biol. Chem. |volume=279 |issue= 17 |pages= 17283–8 |year= 2004 |pmid= 15004027 |doi= 10.1074/jbc.C300549200 |display-authors=etal|doi-access=free }}
*{{cite journal  | vauthors=Ramachandran N, Hainsworth E, Bhullar B |title=Self-assembling protein microarrays. |journal=Science |volume=305 |issue= 5680 |pages= 86–90 |year= 2004 |pmid= 15232106 |doi= 10.1126/science.1097639 |bibcode=2004Sci...305...86R |s2cid=20936301 |display-authors=etal}}
*{{cite journal  | vauthors=Ballabeni A, Melixetian M, Zamponi R |title=Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis. |journal=EMBO J. |volume=23 |issue= 15 |pages= 3122–32 |year= 2005 |pmid= 15257290 |doi= 10.1038/sj.emboj.7600314  | pmc=514931 |display-authors=etal}}
*{{cite journal  | vauthors=Saxena S, Yuan P, Dhar SK |title=A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition. |journal=Mol. Cell |volume=15 |issue= 2 |pages= 245–58 |year= 2004 |pmid= 15260975 |doi= 10.1016/j.molcel.2004.06.045 |display-authors=etal|doi-access=free }}
*{{cite journal  | vauthors=Kulartz M, Knippers R |title=The replicative regulator protein geminin on chromatin in the HeLa cell cycle. |journal=J. Biol. Chem. |volume=279 |issue= 40 |pages= 41686–94 |year= 2004 |pmid= 15284237 |doi= 10.1074/jbc.M405798200 |doi-access= free }}
*{{cite journal  | vauthors=Beausoleil SA, Jedrychowski M, Schwartz D |title=Large-scale characterization of HeLa cell nuclear phosphoproteins. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130–5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101  | pmc=514446 |bibcode=2004PNAS..10112130B |display-authors=etal|doi-access=free }}
{{refend}}

== External links ==
* {{PDBe-KB2|Q9H211|Human DNA replication factor Cdt1}}
* {{PDBe-KB2|Q8R4E9|Mouse DNA replication factor Cdt1}}

{{DNA replication}}

[[Category:Proteins]]
[[Category:DNA replication]]


{{gene-16-stub}}