Biology:DNA replication factor CDT1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
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:

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

  1. "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. 
  2. "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. 
  3. "Entrez Gene: CDT1 chromatin licensing and DNA replication factor 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=81620. 
  4. "CDT1 gene" (in en). https://ghr.nlm.nih.gov/gene/CDT1. 
  5. 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. 
  6. "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. Bibcode2000Sci...290.2309W. 
  7. "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. 
  8. "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. 
  9. "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. Bibcode2000Natur.404..622M. 
  10. "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. 
  11. "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

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.