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Gene Review

Top1  -  topoisomerase (DNA) I

Mus musculus

Synonyms: AI467334, D130064I21Rik, DNA topoisomerase 1, DNA topoisomerase I, Top-1
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Disease relevance of Top1

  • OBJECTIVE: Autoantibodies to DNA topoisomerase I (topo I) are associated with diffuse systemic sclerosis (SSc), appear to be antigen driven, and may be triggered by cryptic epitopes exposed during in vivo topo I fragmentation [1].
  • DNA topoisomerase I--targeted chemotherapy of human colon cancer in xenografts [2].
  • The requirement of mouse DNA topoisomerase IIIalpha during early embryogenesis is discussed in terms of its plausible role in chromosome replication and its interaction with the RecQ/SGS1 family of DNA helicases, whose members include the Bloom's syndrome and the Werner's syndrome gene products [3].
  • Effects of the bifunctional antitumor intercalator ditercalinium on DNA in mouse leukemia L1210 cells and DNA topoisomerase II [4].
  • Previous studies have shown that DNA topoisomerase II enzyme activity and protein levels are reduced in cloned lines of Adriamycin-resistant P388 leukemia cells relative to drug-sensitive cells (Deffie et al., Cancer Res., 49: 58-62, 1989) [5].

High impact information on Top1

  • DNA topoisomerase I, a nuclear enzyme important for solving topological problems arising during DNA replication and for other cellular functions, has been identified as a principal target of a plant alkaloid 20(S)-camptothecin [2].
  • Treatment with DNA topoisomerase II inhibitors accelerated both the rHuTNF-mediated DNA fragmentation and the elevation in TRPM-2 messenger RNA levels [6].
  • On the other hand, polyoma RNA and 5S RNA synthesis were inhibited by novobiocin in a way that suggested the requirement of a DNA topoisomerase II or DNA gyrase activity for the initiation of transcription [7].
  • In vitro transcription by Xenopus oocytes RNA polymerase III requires a DNA topoisomerase II activity [7].
  • Aberrant lamination in the cerebral cortex of mouse embryos lacking DNA topoisomerase IIbeta [8].

Chemical compound and disease context of Top1


Biological context of Top1


Anatomical context of Top1


Associations of Top1 with chemical compounds


Regulatory relationships of Top1


Other interactions of Top1


Analytical, diagnostic and therapeutic context of Top1


  1. Involvement of lysosomal cathepsins in the cleavage of DNA topoisomerase I during necrotic cell death. Pacheco, F.J., Servin, J., Dang, D., Kim, J., Molinaro, C., Daniels, T., Brown-Bryan, T.A., Imoto-Egami, M., Casiano, C.A. Arthritis Rheum. (2005) [Pubmed]
  2. DNA topoisomerase I--targeted chemotherapy of human colon cancer in xenografts. Giovanella, B.C., Stehlin, J.S., Wall, M.E., Wani, M.C., Nicholas, A.W., Liu, L.F., Silber, R., Potmesil, M. Science (1989) [Pubmed]
  3. Mammalian DNA topoisomerase IIIalpha is essential in early embryogenesis. Li, W., Wang, J.C. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  4. Effects of the bifunctional antitumor intercalator ditercalinium on DNA in mouse leukemia L1210 cells and DNA topoisomerase II. Markovits, J., Pommier, Y., Mattern, M.R., Esnault, C., Roques, B.P., Le Pecq, J.B., Kohn, K.W. Cancer Res. (1986) [Pubmed]
  5. Evidence for a mutant allele of the gene for DNA topoisomerase II in adriamycin-resistant P388 murine leukemia cells. Deffie, A.M., Bosman, D.J., Goldenberg, G.J. Cancer Res. (1989) [Pubmed]
  6. Activation of programmed cell death by recombinant human tumor necrosis factor plus topoisomerase II-targeted drugs in L929 tumor cells. Kyprianou, N., Alexander, R.B., Isaacs, J.T. J. Natl. Cancer Inst. (1991) [Pubmed]
  7. In vitro transcription by Xenopus oocytes RNA polymerase III requires a DNA topoisomerase II activity. Glikin, G.C., Blangy, D. EMBO J. (1986) [Pubmed]
  8. Aberrant lamination in the cerebral cortex of mouse embryos lacking DNA topoisomerase IIbeta. Lyu, Y.L., Wang, J.C. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  9. Decreased DNA topoisomerase II in daunorubicin-resistant Ehrlich ascites tumor cells. Friche, E., Danks, M.K., Schmidt, C.A., Beck, W.T. Cancer Res. (1991) [Pubmed]
  10. Inhibition of retrovirus RNA-dependent DNA polymerase by novobiocin and nalidixic acid. Sumiyoshi, Y., Nishikawa, T., Watanabe, T., Kano, K. J. Gen. Virol. (1983) [Pubmed]
  11. Inhibition of protein synthesis reduces the cytotoxicity of 4'-(9-acridinylamino)methanesulfon-m-anisidide without affecting DNA breakage and DNA topoisomerase II in a murine mastocytoma cell line. Schneider, E., Lawson, P.A., Ralph, R.K. Biochem. Pharmacol. (1989) [Pubmed]
  12. Role of DNA intercalation in the inhibition of purified mouse leukemia (L1210) DNA topoisomerase II by 9-aminoacridines. Pommier, Y., Covey, J., Kerrigan, D., Mattes, W., Markovits, J., Kohn, K.W. Biochem. Pharmacol. (1987) [Pubmed]
  13. Ciprofloxacin: mammalian DNA topoisomerase type II poison in vivo. Mukherjee, A., Sen, S., Agarwal, K. Mutat. Res. (1993) [Pubmed]
  14. Cloning of the mouse cDNA encoding DNA topoisomerase I and chromosomal location of the gene. Koiwai, O., Yasui, Y., Sakai, Y., Watanabe, T., Ishii, K., Yanagihara, S., Andoh, T. Gene (1993) [Pubmed]
  15. Genetic mapping of DNA topoisomerase I-related sequences to mouse chromosomes 2 and 14. Kingsmore, S.F., Lo, C.K., Hwang, J., Hui, C.F., Seldin, M.F. Mamm. Genome (1994) [Pubmed]
  16. A novel polypyrimidine antitumor agent FdUMP[10] induces thymineless death with topoisomerase I-DNA complexes. Liao, Z.Y., Sordet, O., Zhang, H.L., Kohlhagen, G., Antony, S., Gmeiner, W.H., Pommier, Y. Cancer Res. (2005) [Pubmed]
  17. Relationship between amine-carboxyboranes and TNF alpha for the regulation of cell growth in different tumor cell lines. Miller, M.C., Woods, C.M., Murphy, M.E., Elkins, A., Spielvogel, B.F., Hall, I.H. Biomed. Pharmacother. (1998) [Pubmed]
  18. DNA topoisomerase I in the mouse central nervous system: Age and sex dependence. Plaschkes, I., Silverman, F.W., Priel, E. J. Comp. Neurol. (2005) [Pubmed]
  19. DNA damage by antitumor acridines mediated by mammalian DNA topoisomerase II. Rowe, T.C., Chen, G.L., Hsiang, Y.H., Liu, L.F. Cancer Res. (1986) [Pubmed]
  20. Proliferation-dependent topoisomerase II content as a determinant of antineoplastic drug action in human, mouse, and Chinese hamster ovary cells. Sullivan, D.M., Latham, M.D., Ross, W.E. Cancer Res. (1987) [Pubmed]
  21. Decreased expression of DNA topoisomerase I in camptothecin-resistant tumor cell lines as determined by a monoclonal antibody. Sugimoto, Y., Tsukahara, S., Oh-hara, T., Isoe, T., Tsuruo, T. Cancer Res. (1990) [Pubmed]
  22. Synergistic enhancement by tumor necrosis factor of in vitro cytotoxicity from chemotherapeutic drugs targeted at DNA topoisomerase II. Alexander, R.B., Nelson, W.G., Coffey, D.S. Cancer Res. (1987) [Pubmed]
  23. Topoisomerase II-mediated DNA damage produced by 4'-(9-acridinylamino)methanesulfon-m-anisidide and related acridines in L1210 cells and isolated nuclei: relation to cytotoxicity. Covey, J.M., Kohn, K.W., Kerrigan, D., Tilchen, E.J., Pommier, Y. Cancer Res. (1988) [Pubmed]
  24. Impairment of Moloney murine leukemia virus integration in a cell line underexpressing DNA topoisomerase II. Bouillé, P., Subra, F., Goulaouic, H., Carteau, S., Auclair, C. Cancer Res. (1995) [Pubmed]
  25. Targeted disruption of the mouse topoisomerase I gene by camptothecin selection. Morham, S.G., Kluckman, K.D., Voulomanos, N., Smithies, O. Mol. Cell. Biol. (1996) [Pubmed]
  26. In vitro and in vivo anti-tumor activity of recombinant mouse tumor necrosis factor (TNF) in a mouse bladder tumor (MBT-2). Bahnson, R.R., Ratliff, T.L. J. Urol. (1990) [Pubmed]
  27. Response of DNA repair enzymes in murine fibrosarcoma, lymphosarcoma and ascites cells following gamma irradiation. Pasupathy, K., Nair, C.K. J. Radiat. Res. (2003) [Pubmed]
  28. Characterization of a DNA topoisomerase IIalpha gene rearrangement in adriamycin-resistant P388 leukemia: expression of a fusion messenger RNA transcript encoding topoisomerase IIalpha and the retinoic acid receptor alpha locus. McPherson, J.P., Brown, G.A., Goldenberg, G.J. Cancer Res. (1993) [Pubmed]
  29. DNA topoisomerase I phosphorylation in murine fibroblasts treated with 12-O-tetradecanoylphorbol-13-acetate and in vitro by protein kinase. Samuels, D.S., Shimizu, N. J. Biol. Chem. (1992) [Pubmed]
  30. RAS mutations in pediatric leukemias with MLL gene rearrangements. Mahgoub, N., Parker, R.I., Hosler, M.R., Close, P., Winick, N.J., Masterson, M., Shannon, K.M., Felix, C.A. Genes Chromosomes Cancer (1998) [Pubmed]
  31. Is DNA topoisomerase II beta a nucleolar protein? Chaly, N., Brown, D.L. J. Cell. Biochem. (1996) [Pubmed]
  32. Establishment and characterization of a mouse FM3A cell mutant resistant to topoisomerase II-inhibitor NC-190. Samata, K., Yamagishi, T., Ichihara, T., Nanaumi, K., Ikeda, T., Ikeya, H., Kuraishi, A., Nakaike, S., Kashiwagi, K., Igarashi, K. Cancer Chemother. Pharmacol. (2002) [Pubmed]
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