DNA replication factor CDT1

Last updated
CDT1
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CDT1 , DUP, RIS2, chromatin licensing and DNA replication factor 1
External IDs OMIM: 605525 MGI: 1914427 HomoloGene: 32650 GeneCards: CDT1
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 Mb Chr 8: 123.29 – 123.3 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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.

Contents

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). [9]

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. [10] 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. [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]

Related Research Articles

<span class="mw-page-title-main">MCM6</span>

DNA replication licensing factor MCM6 is a protein that in humans is encoded by the MCM6 gene. MCM6 is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication.

<span class="mw-page-title-main">Geminin</span> Nuclear protein inhibiting DNA replication

Geminin, DNA replication inhibitor, also known as GMNN, is a protein in humans encoded by the GMNN gene. A nuclear protein present in most eukaryotes and highly conserved across species, numerous functions have been elucidated for geminin including roles in metazoan cell cycle, cellular proliferation, cell lineage commitment, and neural differentiation. One example of its function is the inhibition of Cdt1.

<span class="mw-page-title-main">Eukaryotic DNA replication</span> DNA replication in eukaryotic organisms

Eukaryotic DNA replication is a conserved mechanism that restricts DNA replication to once per cell cycle. Eukaryotic DNA replication of chromosomal DNA is central for the duplication of a cell and is necessary for the maintenance of the eukaryotic genome.

<span class="mw-page-title-main">MCM7</span> Protein-coding gene in the species Homo sapiens

DNA replication licensing factor MCM7 is a protein that in humans is encoded by the MCM7 gene.

<span class="mw-page-title-main">MCM2</span> Protein-coding gene in the species Homo sapiens

DNA replication licensing factor MCM2 is a protein that in humans is encoded by the MCM2 gene.

<span class="mw-page-title-main">MCM3</span> Protein-coding gene in the species Homo sapiens

DNA replication licensing factor MCM3 is a protein that in humans is encoded by the MCM3 gene.

<span class="mw-page-title-main">CDC6</span> Protein-coding gene in the species Homo sapiens

Cell division control protein 6 homolog is a protein that in humans is encoded by the CDC6 gene.

<span class="mw-page-title-main">CUL4A</span> Protein-coding gene in humans

Cullin-4A is a protein that in humans is encoded by the CUL4A gene. CUL4A belongs to the cullin family of ubiquitin ligase proteins and is highly homologous to the CUL4B protein. CUL4A regulates numerous key processes such as DNA repair, chromatin remodeling, spermatogenesis, haematopoiesis and the mitotic cell cycle. As a result, CUL4A has been implicated in several cancers and the pathogenesis of certain viruses including HIV. A component of a CUL4A complex, Cereblon, was discovered to be a major target of the teratogenic agent thalidomide.

<span class="mw-page-title-main">MCM4</span> Protein-coding gene in the species Homo sapiens

DNA replication licensing factor MCM4 is a protein that in humans is encoded by the MCM4 gene.

<span class="mw-page-title-main">DDB1</span> Protein-coding gene in the species Homo sapiens

DNA damage-binding protein 1 is a protein that in humans is encoded by the DDB1 gene.

<span class="mw-page-title-main">ORC2</span> Protein-coding gene in the species Homo sapiens

Origin recognition complex subunit 2 is a protein that is encoded by the ORC2 (ORC2L) gene in humans.

<span class="mw-page-title-main">Cell division cycle 7-related protein kinase</span> Protein-coding gene in the species Homo sapiens

Cell division cycle 7-related protein kinase is an enzyme that in humans is encoded by the CDC7 gene. The Cdc7 kinase is involved in regulation of the cell cycle at the point of chromosomal DNA replication. The gene CDC7 appears to be conserved throughout eukaryotic evolution; this means that most eukaryotic cells have the Cdc7 kinase protein.

<span class="mw-page-title-main">CKS1B</span> Protein-coding gene in the species Homo sapiens

Cyclin-dependent kinases regulatory subunit 1 is a protein that in humans is encoded by the CKS1B gene.

<span class="mw-page-title-main">ORC6</span> Protein-coding gene in the species Homo sapiens

Origin recognition complex subunit 6 is a protein that in humans is encoded by the ORC6 (ORC6L) gene.

<i>NFIC</i> (gene) Protein-coding gene in the species Homo sapiens

Nuclear factor 1 C-type is a protein that in humans is encoded by the NFIC gene.

<span class="mw-page-title-main">MED17</span> Protein-coding gene in the species Homo sapiens

Mediator of RNA polymerase II transcription subunit 17 is an enzyme that in humans is encoded by the MED17 gene.

<span class="mw-page-title-main">Control of chromosome duplication</span>

In cell biology, eukaryotes possess a regulatory system that ensures that DNA replication occurs only once per cell cycle.

<span class="mw-page-title-main">ORC1</span> Protein-coding gene in the species Homo sapiens

Origin recognition complex subunit 1 is a protein that in humans is encoded by the ORC1 gene. It is closely related to CDC6, and both are the same protein in archaea.

<span class="mw-page-title-main">DNA re-replication</span> Undesirable occurrence in eukaryotic cells

DNA re-replication is an undesirable and possibly fatal occurrence in eukaryotic cells in which the genome is replicated more than once per cell cycle. Rereplication is believed to lead to genomic instability and has been implicated in the pathologies of a variety of human cancers. To prevent rereplication, eukaryotic cells have evolved multiple, overlapping mechanisms to inhibit chromosomal DNA from being partially or fully rereplicated in a given cell cycle. These control mechanisms rely on cyclin-dependent kinase (CDK) activity. DNA replication control mechanisms cooperate to prevent the relicensing of replication origins and to activate cell cycle and DNA damage checkpoints. DNA rereplication must be strictly regulated to ensure that genomic information is faithfully transmitted through successive generations.

Zoi Lygerou is a Greek molecular biologist and associate professor at Patras Medical School. Lygerou's works have been published in such journals as the European Journal of Biochemistry, Journal of Cell Science, the Molecular and Cellular Biology journal, Journal of Biological Chemistry, and both Science and Nature journals among others. She is especially known for her work on cell cycle control mechanisms in eukaryotic organisms, and has done research at the University of Patras since 1999. Lygerou has also held positions at the European Molecular Biology Laboratory (EMBL) and at the Imperial Cancer Research Fund in London under Paul Nurse.

References

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  2. 1 2 3 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. doi:10.1242/jcs.115.7.1435. 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. "CDT1 gene". Genetics Home Reference. Retrieved 2018-07-19.
  9. 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.{{cite book}}: CS1 maint: location missing publisher (link)
  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. Bibcode:2000Sci...290.2309W. 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. Bibcode:2000Natur.404..622M. doi:10.1038/35007104. PMID   10766247. S2CID   4416138.
  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