DNA replication factor CDT1

Chromatin licensing and DNA replication factor 1
Identifiers
Symbols	CDT1; DUP; RIS2
External IDs	OMIM: 605525 MGI: 1914427 HomoloGene: 32650 GeneCards: CDT1 Gene
Gene Ontology Molecular function • DNA binding • protein binding Cellular component • nucleus • nucleoplasm • cytosol Biological process • DNA replication checkpoint • G1/S transition of mitotic cell cycle • regulation of transcription involved in G1/S phase of mitotic cell cycle • S phase of mitotic cell cycle • M/G1 transition of mitotic cell cycle • mitotic cell cycle • DNA replication • regulation of S phase of mitotic cell cycle • regulation of DNA-dependent DNA replication initiation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	81620	67177
Ensembl	ENSG00000167513	ENSMUSG00000006585
UniProt	Q9H211	Q8R4E9
RefSeq (mRNA)	NM_030928	NM_026014.3
RefSeq (protein)	NP_112190	NP_080290.3
Location (UCSC)	Chr 16: 88.87 – 88.88 Mb	Chr 8: 125.09 – 125.1 Mb
PubMed search	[1]	[2]

DNA replication factor Cdt1 is a protein that in humans is encoded by the CDT1 gene.^[1][2][3]

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-replicative 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.^[4]

Orthologs

CDT1 belongs to a family of replication proteins conserved from yeast to humans. Examples of orthlogs in other species include:

• S. pombe – cdt1 (cdc10-dependent transcript 1)^[5]
• Drosophila melanogaster – 'double parked' or Dup^[6]
• Xenopus laevis - Cdt1^[7]

Interactions

DNA replication factor CDT1 has been shown to interact with SKP2.^[8] 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 Machida and Dutta, cellylar checkpoint mechanisms monitoring proper initiation of DNA replication, the journal of biological chemistry, 2005, vol 280 number 8)

References

1. ^ Rialland M, Sola F, Santocanale C (Mar 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 (Nov 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". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=81620. 
4. ^ 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. 
5. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=394824. 
6. ^ 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. 
7. ^ 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. 
8. ^ Li, Xianghong; Zhao Qiping, Liao Rong, Sun Peiqing, Wu Xiaohua (Aug. 2003). "The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation". J. Biol. Chem. (United States) 278 (33): 30854–8. doi:10.1074/jbc.C300251200. ISSN 0021-9258. PMID 12840033. 

Further reading

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