Biology:DNA replication factor CDT1
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
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 it, 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:
- S. pombe – CDT1 (CDC10-dependent transcript 1)[7]
- Drosophila melanogaster – 'double parked' or Dup[8]
- Xenopus laevis - CDT1[9]
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
- ↑ "Essential role of human CDT1 in DNA replication and chromatin licensing". J Cell Sci 115 (Pt 7): 1435–40. March 2002. doi:10.1242/jcs.115.7.1435. PMID 11896191.
- ↑ "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. November 2001. doi:10.1074/jbc.M105406200. PMID 11555648.
- ↑ "Entrez Gene: CDT1 chromatin licensing and DNA replication factor 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=81620.
- ↑ "CDT1 gene" (in en). https://ghr.nlm.nih.gov/gene/CDT1.
- ↑ 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.
- ↑ "Inhibition of eukaryotic DNA replication by geminin binding to Cdt1". Science 290 (5500): 2309–12. December 2000. doi:10.1126/science.290.5500.2309. PMID 11125146. Bibcode: 2000Sci...290.2309W.
- ↑ "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. January 1994. doi:10.1002/j.1460-2075.1994.tb06277.x. PMID 8313888.
- ↑ "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. May 2006. doi:10.1074/jbc.M600575200. PMID 16531405.
- ↑ "XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis.". Nature 404 (6778): 622–5. April 2000. doi:10.1038/35007104. PMID 10766247. Bibcode: 2000Natur.404..622M.
- ↑ "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. 2003. doi:10.1074/jbc.C300251200. PMID 12840033.
- ↑ "Cellular checkpoint mechanisms monitoring proper initiation of DNA replication". J. Biol. Chem. 280 (8): 6253–6. 2005. doi:10.1074/jbc.R400037200. PMID 15591064.
Further reading
- "Cdt1 interactions in the licensing process: a model for dynamic spatiotemporal control of licensing.". Cell Cycle 6 (13): 1549–52. 2007. doi:10.4161/cc.6.13.4455. PMID 17598984.
- "A "double adaptor" method for improved shotgun library construction.". Anal. Biochem. 236 (1): 107–13. 1996. doi:10.1006/abio.1996.0138. PMID 8619474.
- "Large-scale concatenation cDNA sequencing.". Genome Res. 7 (4): 353–8. 1997. doi:10.1101/gr.7.4.353. PMID 9110174.
- "The Cdt1 protein is required to license DNA for replication in fission yeast.". Nature 404 (6778): 625–8. 2000. doi:10.1038/35007110. PMID 10766248. Bibcode: 2000Natur.404..625N.
- "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. 2000. doi:10.1101/gad.14.14.1765. PMID 10898791.
- "Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.". Science 290 (5500): 2309–12. 2001. doi:10.1126/science.290.5500.2309. PMID 11125146. Bibcode: 2000Sci...290.2309W.
- "Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity.". J. Biol. Chem. 277 (43): 40871–80. 2002. doi:10.1074/jbc.M206202200. PMID 12192004.
- "Regulation of CDC6, geminin, and CDT1 in human cells that undergo polyploidization.". Mol. Biol. Cell 13 (11): 3989–4000. 2003. doi:10.1091/mbc.E02-04-0217. PMID 12429841.
- "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. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "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. 2003. doi:10.1074/jbc.C300251200. PMID 12840033.
- "The regulated association of Cdt1 with minichromosome maintenance proteins and Cdc6 in mammalian cells.". J. Biol. Chem. 279 (10): 9625–33. 2004. doi:10.1074/jbc.M311933200. PMID 14672932.
- "Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding.". J. Biol. Chem. 279 (19): 19691–7. 2004. doi:10.1074/jbc.M313175200. PMID 14993212.
- "Cyclin-dependent kinases phosphorylate human Cdt1 and induce its degradation.". J. Biol. Chem. 279 (17): 17283–8. 2004. doi:10.1074/jbc.C300549200. PMID 15004027.
- "Self-assembling protein microarrays.". Science 305 (5680): 86–90. 2004. doi:10.1126/science.1097639. PMID 15232106. Bibcode: 2004Sci...305...86R.
- "Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis.". EMBO J. 23 (15): 3122–32. 2005. doi:10.1038/sj.emboj.7600314. PMID 15257290.
- "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. 2004. doi:10.1016/j.molcel.2004.06.045. PMID 15260975.
- "The replicative regulator protein geminin on chromatin in the HeLa cell cycle.". J. Biol. Chem. 279 (40): 41686–94. 2004. doi:10.1074/jbc.M405798200. PMID 15284237.
- "Large-scale characterization of HeLa cell nuclear phosphoproteins.". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. 2004. doi:10.1073/pnas.0404720101. PMID 15302935. Bibcode: 2004PNAS..10112130B.
External links
- Overview of all the structural information available in the PDB for UniProt: Q9H211 (Human DNA replication factor Cdt1) at the PDBe-KB.
- Overview of all the structural information available in the PDB for UniProt: Q8R4E9 (Mouse DNA replication factor Cdt1) at the PDBe-KB.
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