DNA replication factor CDT1

DNA replication factor CDT1
Chromatin licensing and DNA replication factor 1
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_026014.3
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]

Contents

Orthologs

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

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



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