DNA replication factor CDT1

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CDT1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCDT1, DUP, RIS2, chromatin licensing and DNA replication factor 1
External IDsOMIM: 605525 MGI: 1914427 HomoloGene: 32650 GeneCards: CDT1
Gene location (Human)
Chromosome 16 (human)
Chr.Chromosome 16 (human)[1]
Chromosome 16 (human)
Genomic location for CDT1
Genomic location for CDT1
Band16q24.3Start88,803,789 bp[1]
End88,809,258 bp[1]
RNA expression pattern
PBB GE CDT1 209832 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_030928

NM_026014

RefSeq (protein)

NP_112190

NP_080290

Location (UCSC)Chr 16: 88.8 – 88.81 MbChr 8: 122.57 – 122.57 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

CDT1 (Chromatin licensing and DNA replication factor 1) is a protein that in humans is encoded by the CDT1 gene.[5][6][7][8] It is a licensing factor that functions to limit DNA from replicating more than once per cell cycle.

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 its, and by SCFSKP2, which ubiquinates the protein to tag it for proteasomal degradation.[10] This regulation is important in preventing relicensing, thus ensuring that DNA is only replicated once per cell cycle.

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] 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.[15]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000167513 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000006585 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ 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.
  7. ^ "Entrez Gene: CDT1 chromatin licensing and DNA replication factor 1".
  8. ^ Reference, Genetics Home. "CDT1 gene". Genetics Home Reference. Retrieved 2018-07-19.
  9. ^ Hoffman, Ronald; ), Edward J. Benz (Jr; 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ 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]