The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CCNO  -  cyclin O

Homo sapiens

Synonyms: CCNU, CILD29, Cyclin-O, FLJ22422, UDG2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CCNU

  • We have previously reported that the host uracil DNA glycosylase enzyme UNG2 is packaged into HIV-1 viral particles via a specific association with the integrase domain of the Gag-Pol precursor [1].
  • We demonstrate that virion-associated UNG2 catalytic activity can be replaced by the packaging of heterologous dUTPase into virion, indicating that UNG2 acts to counteract dUTP misincorporation in the viral genome [2].
  • Our findings indicate that pharmacologic strategies aimed toward blocking UNG2 packaging should be explored as potential HIV/AIDS therapeutics [2].
  • In this study, we investigated whether UNG2 was packaged into two phylogenetically closely related primate lentiviruses, HIV-2(ROD) and SIV(MAC239) [3].
  • We then showed by Western blotting that highly purified HIV-2 and SIV(MAC) viral particles did not incorporate host UNG2, contrasting with the presence of UNG2 in HIV-1 viral particles [3].

High impact information on CCNU

  • Therefore, HIV-1 prevents incorporation of dUTP in viral cDNA by UNG2-mediated uracil excision followed by a dNTP-dependent, reverse transcriptase-mediated endonucleolytic cleavage and finally by strand-displacement polymerization [2].
  • Thus, PPM1D may inhibit BER by dephosphorylating UNG2 to facilitate its inactivation after completion of DNA repair [4].
  • We have identified UNG2 phosphorylation sites at threonines 6 and 126 that exhibit enhanced phosphorylation following UV irradiation [4].
  • PPM1D dephosphorylation of UNG2 at phosphothreonine 6 is associated with reduced UNG2 activity [4].
  • Our results may explain why SMUG1 cannot compensate the UNG2 deficiency in human B cells, and are fully consistent with the DNA deamination model that requires active nuclear UNG2 [5].

Biological context of CCNU


Anatomical context of CCNU


Associations of CCNU with chemical compounds

  • The UV-induced phosphorylated forms of UNG2 are more active than nonphosphorylated forms in mediating uracil-associated DNA cleavage [4].
  • The resulting triskelion oximes were directly screened for inhibitory activity and the most potent of these showed micromolar binding affinities to UNG2 and dUTPase [16].
  • Human nuclear uracil DNA glycosylase (UNG2) and deoxyuridine triphosphate nucleotidohydrolase (dUTPase) are the primary enzymes that prevent the incorporation and accumulation of deoxyuridine in genomic DNA [16].
  • We propose a model in which hUNG2 is responsible for both prereplicative removal of deaminated cytosine and postreplicative removal of misincorporated uracil at the replication fork [17].

Regulatory relationships of CCNU


Other interactions of CCNU

  • Here, we demonstrate that PPM1D interacts with the nuclear isoform of uracil DNA glycosylase, UNG2, and suppresses base excision repair (BER) [4].
  • Association of UNG2 with PCNA was abolished by the addition of 100 mM NaCl, and significantly decreased in the presence of 10 mM MgCl(2) [18].
  • We report that the major nuclear uracil-DNA glycosylase (UNG2) increases in S phase, during which it co-localizes with incorporated BrdUrd in replication foci [19].
  • Synthesis and high-throughput evaluation of triskelion uracil libraries for inhibition of human dUTPase and UNG2 [16].
  • RESULTS: Three novel missense variants were identified NEIL2 C367A, TDG3 A196G and UNG2 C262T in patients, which were not observed in 188 healthy control DNAs [20].

Analytical, diagnostic and therapeutic context of CCNU

  • UNG2 co-eluted with PCNA during size exclusion chromatography and bound to a PCNA affinity column [18].
  • SDS-PAGE analysis of Ugi affinity-purified and immunoprecipitated UDG2 reveals two closely migrating phosphate-containing species, indicating that UDG2 either contains multiple phosphorylation sites (resulting in heterogeneous migration) or that two distinct forms of UDG2 exist in the cell [21].


  1. Functional role of HIV-1 virion-associated uracil DNA glycosylase 2 in the correction of G:U mispairs to G:C pairs. Priet, S., Navarro, J.M., Gros, N., Querat, G., Sire, J. J. Biol. Chem. (2003) [Pubmed]
  2. HIV-1-associated uracil DNA glycosylase activity controls dUTP misincorporation in viral DNA and is essential to the HIV-1 life cycle. Priet, S., Gros, N., Navarro, J.M., Boretto, J., Canard, B., Quérat, G., Sire, J. Mol. Cell (2005) [Pubmed]
  3. Differential incorporation of uracil DNA glycosylase UNG2 into HIV-1, HIV-2, and SIV(MAC) viral particles. Priet, S., Navarro, J.M., Gros, N., Quérat, G., Sire, J. Virology (2003) [Pubmed]
  4. The p53-induced oncogenic phosphatase PPM1D interacts with uracil DNA glycosylase and suppresses base excision repair. Lu, X., Bocangel, D., Nannenga, B., Yamaguchi, H., Appella, E., Donehower, L.A. Mol. Cell (2004) [Pubmed]
  5. B cells from hyper-IgM patients carrying UNG mutations lack ability to remove uracil from ssDNA and have elevated genomic uracil. Kavli, B., Andersen, S., Otterlei, M., Liabakk, N.B., Imai, K., Fischer, A., Durandy, A., Krokan, H.E., Slupphaug, G. J. Exp. Med. (2005) [Pubmed]
  6. Uracil DNA glycosylase is dispensable for human immunodeficiency virus type 1 replication and does not contribute to the antiviral effects of the cytidine deaminase Apobec3G. Kaiser, S.M., Emerman, M. J. Virol. (2006) [Pubmed]
  7. A fission yeast homologue of the human uracil-DNA-glycosylase and their roles in causing DNA damage after overexpression. Elder, R.T., Zhu, X., Priet, S., Chen, M., Yu, M., Navarro, J.M., Sire, J., Zhao, Y. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  8. Molecular mechanism of PCNA-dependent base excision repair. Matsumoto, Y. Prog. Nucleic Acid Res. Mol. Biol. (2001) [Pubmed]
  9. Reversion of the lethal phenotype of an HIV-1 integrase mutant virus by overexpression of the same integrase mutant protein. Priet, S., Navarro, J.M., Quérat, G., Sire, J. J. Biol. Chem. (2003) [Pubmed]
  10. Mimicking damaged DNA with a small molecule inhibitor of human UNG2. Krosky, D.J., Bianchet, M.A., Seiple, L., Chung, S., Amzel, L.M., Stivers, J.T. Nucleic Acids Res. (2006) [Pubmed]
  11. Regulation of expression of nuclear and mitochondrial forms of human uracil-DNA glycosylase. Haug, T., Skorpen, F., Aas, P.A., Malm, V., Skjelbred, C., Krokan, H.E. Nucleic Acids Res. (1998) [Pubmed]
  12. Repair of U/G and U/A in DNA by UNG2-associated repair complexes takes place predominantly by short-patch repair both in proliferating and growth-arrested cells. Akbari, M., Otterlei, M., Peña-Diaz, J., Aas, P.A., Kavli, B., Liabakk, N.B., Hagen, L., Imai, K., Durandy, A., Slupphaug, G., Krokan, H.E. Nucleic Acids Res. (2004) [Pubmed]
  13. Vpr-mediated incorporation of UNG2 into HIV-1 particles is required to modulate the virus mutation rate and for replication in macrophages. Chen, R., Le Rouzic, E., Kearney, J.A., Mansky, L.M., Benichou, S. J. Biol. Chem. (2004) [Pubmed]
  14. Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Recruits Uracil DNA Glycosylase 2 at the Terminal Repeats and Is Important for Latent Persistence of the Virus. Verma, S.C., Bajaj, B.G., Cai, Q., Si, H., Seelhammer, T., Robertson, E.S. J. Virol. (2006) [Pubmed]
  15. The cyclin-like uracil DNA glycosylase (UDG) of murine oocytes and its relationship to human and chimpanzee homologues. Hirst, R., Gosden, R., Miller, D. Gene (2006) [Pubmed]
  16. Synthesis and high-throughput evaluation of triskelion uracil libraries for inhibition of human dUTPase and UNG2. Jiang, Y.L., Chung, S., Krosky, D.J., Stivers, J.T. Bioorg. Med. Chem. (2006) [Pubmed]
  17. hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup. Kavli, B., Sundheim, O., Akbari, M., Otterlei, M., Nilsen, H., Skorpen, F., Aas, P.A., Hagen, L., Krokan, H.E., Slupphaug, G. J. Biol. Chem. (2002) [Pubmed]
  18. Physical and functional interaction of human nuclear uracil-DNA glycosylase with proliferating cell nuclear antigen. Ko, R., Bennett, S.E. DNA Repair (Amst.) (2005) [Pubmed]
  19. Post-replicative base excision repair in replication foci. Otterlei, M., Warbrick, E., Nagelhus, T.A., Haug, T., Slupphaug, G., Akbari, M., Aas, P.A., Steinsbekk, K., Bakke, O., Krokan, H.E. EMBO J. (1999) [Pubmed]
  20. Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial colorectal cancer predisposition. Broderick, P., Bagratuni, T., Vijayakrishnan, J., Lubbe, S., Chandler, I., Houlston, R.S. BMC Cancer (2006) [Pubmed]
  21. Affinity purification and comparative analysis of two distinct human uracil-DNA glycosylases. Caradonna, S., Ladner, R., Hansbury, M., Kosciuk, M., Lynch, F., Muller, S. Exp. Cell Res. (1996) [Pubmed]
WikiGenes - Universities