DNA replication factor CDT1

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Chromatin licensing and DNA replication factor 1
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CDT1 ; DUP; RIS2
External IDs OMIM605525 MGI1914427 HomoloGene32650 GeneCards: CDT1 Gene
RNA expression pattern
PBB GE CDT1 209832 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 81620 67177
Ensembl ENSG00000167513 ENSMUSG00000006585
UniProt Q9H211 Q8R4E9
RefSeq (mRNA) NM_030928 NM_026014
RefSeq (protein) NP_112190 NP_080290
Location (UCSC) Chr 16:
88.87 – 88.88 Mb
Chr 8:
122.57 – 122.57 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-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.[4]

Orthologs[edit]

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

Interactions[edit]

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.[9]

References[edit]

  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. ^ 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. 
  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 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. 
  9. ^ 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]