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Gene Review

TOP1  -  topoisomerase (DNA) I

Homo sapiens

Synonyms: DNA topoisomerase 1, DNA topoisomerase I
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Disease relevance of TOP1


Psychiatry related information on TOP1

  • The cells of an ataxia-oculomotor apraxia type 1 (AOA1) patient, homozygous for a new aprataxin mutation (T739C), were treated with camptothecin, an inhibitor of DNA topoisomerase I which induces DNA single-strand breaks [5].

High impact information on TOP1


Chemical compound and disease context of TOP1


Biological context of TOP1

  • The chromosomal location of the gene has been mapped to the long arm of chromosome 20, in the region q12-13.2, by hybridization of a radioactively labeled TOP1 cDNA probe to human metaphase chromosomes and to a panel of rodent-human somatic hybrids retaining overlapping subsets of human chromosomes [15].
  • These results indicate that NUP98 is a recurrent target in therapy-related malignancies, and that TOP1 is a previously unrecognized target for chromosomal translocations [1].
  • The 26S proteasome inhibitor MG132 was shown to inhibit CPT-induced down-regulation of TOP1 in BT474 cells and selectively sensitized BT474 but not ZR-75-1 cells to CPT-induced cytotoxicity and apoptosis [3].
  • In an effort to identify potential regulators of TOP1 activity, the transcriptional activity of a TOP1 pseudogene in chromosome 1 was studied [16].
  • In the aggregate, these results suggest that CPT-induced down-regulation of TOP1 could be an important parameter for determining CPT sensitivity/resistance in tumor cells [3].

Anatomical context of TOP1

  • Using truncated versions that direct BTBD2 and TOP1 to the same cellular compartment, either the nucleus or the cytoplasm, co-localization was demonstrated in co-transfected Hela cells [17].
  • Furthermore, DB-67 exhibited substantially less cytotoxicity and radiosensitization activity in the TOP1 mutant Chinese hamster lung fibroblast DC3F/C-10 cells than in their parental DC3F cells [18].
  • During our search for additional cellular targets of Tax using a yeast two-hybrid screening system, we isolated a cDNA encoding human DNA topoisomerase I. Tax was demonstrated to bind to topoisomerase I in vitro, and the Tax-topoisomerase I complex was also detected in HTLV-1-infected T-cells by immunoprecipitation [10].
  • DNA topoisomerase I and II expression in drug resistant germ cell tumours [19].
  • The expression of DNA topoisomerase I and II alpha were therefore assessed immunohistochemically in a range of testicular tumours, especially those with persistent malignant elements on retroperitoneal lymph node dissection [19].

Associations of TOP1 with chemical compounds


Physical interactions of TOP1

  • DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution [25].
  • MLL-SEPTIN6 fusion recurs in novel translocation of chromosomes 3, X, and 11 in infant acute myelomonocytic leukaemia and in t(X;11) in infant acute myeloid leukaemia, and MLL genomic breakpoint in complex MLL-SEPTIN6 rearrangement is a DNA topoisomerase II cleavage site [26].
  • We now report that cdc2 kinase forms stable molecular complexes with the nuclear enzyme DNA topoisomerase II, which is associated with marked stimulation of both DNA binding and catalytic activity of topoisomerase II, albeit in a phosphorylation-independent manner [27].
  • Therefore, stabilization of the DNA-topoisomerase cleavable complexes may be essential in the selectivity of cell kill during S phase [28].
  • In preclinical studies, synergy was observed between tumor necrosis factor-alpha (TNF-alpha) and agents that interact with DNA topoisomerase II, such as actinomycin D (Act D) [29].

Enzymatic interactions of TOP1


Regulatory relationships of TOP1


Other interactions of TOP1


Analytical, diagnostic and therapeutic context of TOP1


  1. The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion. Ahuja, H.G., Felix, C.A., Aplan, P.D. Blood (1999) [Pubmed]
  2. NUP98-topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation. Gurevich, R.M., Aplan, P.D., Humphries, R.K. Blood (2004) [Pubmed]
  3. Ubiquitin/26S proteasome-mediated degradation of topoisomerase I as a resistance mechanism to camptothecin in tumor cells. Desai, S.D., Li, T.K., Rodriguez-Bauman, A., Rubin, E.H., Liu, L.F. Cancer Res. (2001) [Pubmed]
  4. Both NUP98/TOP1 and TOP1/NUP98 transcripts are detected in a de novo AML with t(11;20)(p15;q11). Iwase, S., Akiyama, N., Sekikawa, T., Saito, S., Arakawa, Y., Horiguchi-Yamada, J., Yamada, H. Genes Chromosomes Cancer (2003) [Pubmed]
  5. The novel human gene aprataxin is directly involved in DNA single-strand-break repair. Mosesso, P., Piane, M., Palitti, F., Pepe, G., Penna, S., Chessa, L. Cell. Mol. Life Sci. (2005) [Pubmed]
  6. Histone deacetylase interacts directly with DNA topoisomerase II. Tsai, S.C., Valkov, N., Yang, W.M., Gump, J., Sullivan, D., Seto, E. Nat. Genet. (2000) [Pubmed]
  7. Conservation of structure and mechanism between eukaryotic topoisomerase I and site-specific recombinases. Cheng, C., Kussie, P., Pavletich, N., Shuman, S. Cell (1998) [Pubmed]
  8. Rapid induction of c-fos transcription reveals quantitative linkage of RNA polymerase II and DNA topoisomerase I enzyme activities. Stewart, A.F., Herrera, R.E., Nordheim, A. Cell (1990) [Pubmed]
  9. Localization of a type II DNA topoisomerase to two sites at the periphery of the kinetoplast DNA of Crithidia fasciculata. Melendy, T., Sheline, C., Ray, D.S. Cell (1988) [Pubmed]
  10. HTLV-1 tax oncoprotein binds to DNA topoisomerase I and inhibits its catalytic activity. Suzuki, T., Uchida-Toita, M., Andoh, T., Yoshida, M. Virology (2000) [Pubmed]
  11. Camptothecin resistance involving steps subsequent to the formation of protein-linked DNA breaks in human camptothecin-resistant KB cell lines. Beidler, D.R., Chang, J.Y., Zhou, B.S., Cheng, Y.C. Cancer Res. (1996) [Pubmed]
  12. Two independent amsacrine-resistant human myeloid leukemia cell lines share an identical point mutation in the 170 kDa form of human topoisomerase II. Lee, M.S., Wang, J.C., Beran, M. J. Mol. Biol. (1992) [Pubmed]
  13. Doxorubicin and gamma rays increase the level of DNA topoisomerase IIalpha in nuclei of normal and xeroderma pigmentosum fibroblasts. Thielmann, H.W., Popanda, O. J. Cancer Res. Clin. Oncol. (1998) [Pubmed]
  14. Ceramide triggers caspase activation during gamma-radiation-induced apoptosis of human glioma cells lacking functional p53. Hara, S., Nakashima, S., Kiyono, T., Sawada, M., Yoshimura, S., Iwama, T., Sakai, N. Oncol. Rep. (2004) [Pubmed]
  15. Human DNA topoisomerase I is encoded by a single-copy gene that maps to chromosome region 20q12-13.2. Juan, C.C., Hwang, J.L., Liu, A.A., Whang-Peng, J., Knutsen, T., Huebner, K., Croce, C.M., Zhang, H., Wang, J.C., Liu, L.F. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  16. Identification of antisense RNA transcripts from a human DNA topoisomerase I pseudogene. Zhou, B.S., Beidler, D.R., Cheng, Y.C. Cancer Res. (1992) [Pubmed]
  17. Characterization of BTBD1 and BTBD2, two similar BTB-domain-containing Kelch-like proteins that interact with Topoisomerase I. Xu, L., Yang, L., Hashimoto, K., Anderson, M., Kohlhagen, G., Pommier, Y., D'Arpa, P. BMC Genomics (2002) [Pubmed]
  18. Silatecan DB-67 is a novel DNA topoisomerase I-targeted radiation sensitizer. Chen, A.Y., Shih, S.J., Garriques, L.N., Rothenberg, M.L., Hsiao, M., Curran, D.P. Mol. Cancer Ther. (2005) [Pubmed]
  19. DNA topoisomerase I and II expression in drug resistant germ cell tumours. Berney, D.M., Shamash, J., Gaffney, J., Jordan, S., Oliver, R.T. Br. J. Cancer (2002) [Pubmed]
  20. Elevated expression levels of NCOA3, TOP1, and TFAP2C in breast tumors as predictors of poor prognosis. Zhao, C., Yasui, K., Lee, C.J., Kurioka, H., Hosokawa, Y., Oka, T., Inazawa, J. Cancer (2003) [Pubmed]
  21. Inhibition of human tyrosyl-DNA phosphodiesterase by aminoglycoside antibiotics and ribosome inhibitors. Liao, Z., Thibaut, L., Jobson, A., Pommier, Y. Mol. Pharmacol. (2006) [Pubmed]
  22. Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin. Fujimori, A., Harker, W.G., Kohlhagen, G., Hoki, Y., Pommier, Y. Cancer Res. (1995) [Pubmed]
  23. The RNA-splicing factor PSF/p54 controls DNA-topoisomerase I activity by a direct interaction. Straub, T., Grue, P., Uhse, A., Lisby, M., Knudsen, B.R., Tange, T.O., Westergaard, O., Boege, F. J. Biol. Chem. (1998) [Pubmed]
  24. topors, a p53 and topoisomerase I-binding RING finger protein, is a coactivator of p53 in growth suppression induced by DNA damage. Lin, L., Ozaki, T., Takada, Y., Kageyama, H., Nakamura, Y., Hata, A., Zhang, J.H., Simonds, W.F., Nakagawara, A., Koseki, H. Oncogene (2005) [Pubmed]
  25. DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution. Durrieu, F., Samejima, K., Fortune, J.M., Kandels-Lewis, S., Osheroff, N., Earnshaw, W.C. Curr. Biol. (2000) [Pubmed]
  26. MLL-SEPTIN6 fusion recurs in novel translocation of chromosomes 3, X, and 11 in infant acute myelomonocytic leukaemia and in t(X;11) in infant acute myeloid leukaemia, and MLL genomic breakpoint in complex MLL-SEPTIN6 rearrangement is a DNA topoisomerase II cleavage site. Slater, D.J., Hilgenfeld, E., Rappaport, E.F., Shah, N., Meek, R.G., Williams, W.R., Lovett, B.D., Osheroff, N., Autar, R.S., Ried, T., Felix, C.A. Oncogene (2002) [Pubmed]
  27. Recruitment of cdc2 kinase by DNA topoisomerase II is coupled to chromatin remodeling. Escargueil, A.E., Plisov, S.Y., Skladanowski, A., Borgne, A., Meijer, L., Gorbsky, G.J., Larsen, A.K. FASEB J. (2001) [Pubmed]
  28. Cytostatic and cytotoxic effects of fostriecin on human promyelocytic HL-60 and lymphocytic MOLT-4 leukemic cells. Hotz, M.A., Del Bino, G., Lassota, P., Traganos, F., Darzynkiewicz, Z. Cancer Res. (1992) [Pubmed]
  29. Phase I study of tumor necrosis factor-alpha and actinomycin D in pediatric patients with cancer: a Children's Cancer Group study. Seibel, N.L., Dinndorf, P.A., Bauer, M., Sondel, P.M., Hammond, G.D., Reaman, G.H. Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy. (1994) [Pubmed]
  30. Casein kinase II catalyzes a mitotic phosphorylation on threonine 1342 of human DNA topoisomerase IIalpha, which is recognized by the 3F3/2 phosphoepitope antibody. Daum, J.R., Gorbsky, G.J. J. Biol. Chem. (1998) [Pubmed]
  31. Fusion of the nucleoporin gene, NUP98, and the putative RNA helicase gene, DDX10, by inversion 11 (p15q22) chromosome translocation in a patient with etoposide-related myelodysplastic syndrome. Nakao, K., Nishino, M., Takeuchi, K., Iwata, M., Kawano, A., Arai, Y., Ohki, M. Intern. Med. (2000) [Pubmed]
  32. Assessment of ATM phosphorylation on Ser-1981 induced by DNA topoisomerase I and II inhibitors in relation to Ser-139-histone H2AX phosphorylation, cell cycle phase, and apoptosis. Kurose, A., Tanaka, T., Huang, X., Halicka, H.D., Traganos, F., Dai, W., Darzynkiewicz, Z. Cytometry. Part A : the journal of the International Society for Analytical Cytology. (2005) [Pubmed]
  33. PSF/p54(nrb) stimulates "jumping" of DNA topoisomerase I between separate DNA helices. Straub, T., Knudsen, B.R., Boege, F. Biochemistry (2000) [Pubmed]
  34. Tyrosyl-DNA phosphodiesterase (Tdp1) participates in the repair of Top2-mediated DNA damage. Nitiss, K.C., Malik, M., He, X., White, S.W., Nitiss, J.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  35. Assembly of a polymeric chain of SUMO1 on human topoisomerase I in vitro. Yang, M., Hsu, C.T., Ting, C.Y., Liu, L.F., Hwang, J. J. Biol. Chem. (2006) [Pubmed]
  36. A TaqI RFLP at the human TOP1 pseudogene locus on chromosome 22q11.2-13.1 (TOP1P2). Auerbach, A.D., Allen, R.G., Mann, W.R. Nucleic Acids Res. (1991) [Pubmed]
  37. Expression of NUP98/TOP1, but not of TOP1/NUP98, in a treatment-related myelodysplastic syndrome with t(10;20;11)(q24;q11;p15). Panagopoulos, I., Fioretos, T., Isaksson, M., Larsson, G., Billström, R., Mitelman, F., Johansson, B. Genes Chromosomes Cancer (2002) [Pubmed]
  38. Potential role for DNA topoisomerase II poisons in the generation of t(11;20)(p15;q11) translocations. Ahuja, H.G., Felix, C.A., Aplan, P.D. Genes Chromosomes Cancer (2000) [Pubmed]
  39. Generation of the NUP98-TOP1 fusion transcript by the t(11;20) (p15;q11) in a case of acute monocytic leukemia. Chen, S., Xue, Y., Chen, Z., Guo, Y., Wu, Y., Pan, J. Cancer Genet. Cytogenet. (2003) [Pubmed]
  40. Molecular cloning of a cDNA of a camptothecin-resistant human DNA topoisomerase I and identification of mutation sites. Tamura, H., Kohchi, C., Yamada, R., Ikeda, T., Koiwai, O., Patterson, E., Keene, J.D., Okada, K., Kjeldsen, E., Nishikawa, K. Nucleic Acids Res. (1991) [Pubmed]
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