Protein-coding gene in the species Homo sapiens
CDT1 (Chromatin licensing and DNA replication factor 1) is a protein that in humans is encoded by the CDT1 gene .[5] [6] [7] [8]
Role in pre-replication complexes [ edit ] 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).[9]
The activity of CDT1 during the cell cycle is tightly regulated during the S phase by the protein geminin , which inhibits it, and by SCFSKP2 , which ubiquinates the protein to tag it for proteasomal degradation.[10]
Orthologs [ edit ] CDT1 belongs to a family of replication proteins conserved from yeast to humans. Examples of orthologs in other species include:
Interactions [ edit ] DNA replication factor CDT1 has been shown to interact with SKP2 .[14] 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.[15]
References [ edit ]
^ a b c GRCh38: Ensembl release 89: ENSG00000167513 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000006585 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ 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. doi :10.1242/jcs.115.7.1435 . PMID 11896191 . ^ 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 . ^ "Entrez Gene: CDT1 chromatin licensing and DNA replication factor 1" .^ "CDT1 gene" . Genetics Home Reference . Retrieved 2018-07-19 .^ Hoffman, Ronald; Benz Jr., Edward J.; Silberstein, Leslie E.; Heslop, Helen; Weitz, Jeffrey I.; Anastasi, John; Salama, Mohamed E.; Abutalib, Syed A. (2018). 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 . {{cite book }}: CS1 maint: location missing publisher (link )^ 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. Bibcode :2000Sci...290.2309W . doi :10.1126/science.290.5500.2309 . PMID 11125146 . ^ 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. doi :10.1002/j.1460-2075.1994.tb06277.x . PMC 394824 PMID 8313888 . ^ 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 . ^ 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. Bibcode :2000Natur.404..622M . doi :10.1038/35007104 . PMID 10766247 . S2CID 4416138 . ^ 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 . ^ 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 [ edit ]
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 . 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. Bibcode :2000Natur.404..625N . doi :10.1038/35007110 . PMID 10766248 . S2CID 205005540 . 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. doi :10.1101/gad.14.14.1765 . PMC 316778 PMID 10898791 . Wohlschlegel JA, Dwyer BT, Dhar SK, et al. (2001). "Inhibition of eukaryotic DNA replication by geminin binding to Cdt1". Science . 290 (5500): 2309–12. Bibcode :2000Sci...290.2309W . 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 . 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. Bibcode :2002PNAS...9916899M . doi :10.1073/pnas.242603899 PMC 139241 PMID 12477932 . 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. Bibcode :2004Sci...305...86R . doi :10.1126/science.1097639 . PMID 15232106 . S2CID 20936301 . 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 . 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. Bibcode :2004PNAS..10112130B . doi :10.1073/pnas.0404720101 PMC 514446 PMID 15302935 .
External links [ edit ] Overview of all the structural information available in the PDB for UniProt : Q9H211 PDBe-KB .
Overview of all the structural information available in the PDB for UniProt : Q8R4E9 PDBe-KB .
