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Gene Review

TOP3A  -  topoisomerase (DNA) III alpha

Homo sapiens

Synonyms: DNA topoisomerase 3-alpha, DNA topoisomerase III alpha, TOP3, ZGRF7
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Disease relevance of TOP3A


High impact information on TOP3A

  • Both pCAT4.5 and an antisense hTOP3 construct were able to inhibit spontaneous and radiation-induced apoptosis in A-T fibroblasts, whereas overexpression of a full-length hTOP3 cDNA did not [2].
  • Furthermore, functional correction of hyper-recombination in A-T cells by CAT4.5 supports the hypothesis that the hTOP3 topoisomerase is involved in the control of genomic stability, perhaps in concert with the Bloom or Werner syndrome DNA helicases [2].
  • Screening of a panel of human-rodent somatic hybrids and fluorescence in situ hybridization of cloned TOP3 genomic DNA to metaphase chromosomes indicate that human TOP3 is a single-copy gene located at chromosome 17p11.2-12 [3].
  • Crossovers are associated with long gene conversion tracts, suggesting a model in which Sgs1 helicase catalyzes reverse branch migration and convergence of double HJs for noncrossover resolution by Top3 [4].
  • Top3 processes recombination intermediates and modulates checkpoint activity after DNA damage [5].

Biological context of TOP3A

  • Transient expression of a luciferase reporter gene under the control of serially deleted 5'-flanking sequences revealed that the 52-base pair region from -326 to -275 upstream of the transcription initiation site includes a positive cis-acting element(s) for the efficient expression of hTOP3 gene [1].
  • The hTOP3 gene promoter is moderately high in GC content and lacks a canonical TATA box, suggesting that hTOP3 promoter has overall similarity to promoters of a number of housekeeping genes [1].
  • We report that the gene for topoisomerase III (hTOP3) is commonly deleted in SMS patients and maps between D17S447 and D17S258 on the short arm of chromosome 17 [6].
  • Our studies suggest that haploinsufficiency of hTOP3 does not have a major impact on the behavior of cells from SMS patients and may not play a significant role in the SMS phenotype [6].
  • Our studies indicate that hemizygosity for hTOP3 does not appreciably affect cell-cycle kinetics or activation of ionizing radiation-sensitive cell-cycle checkpoints [6].

Anatomical context of TOP3A

  • When HeLa cells were transiently transfected with a mutant construct which had disabled both YY1- and USF1-binding sites, the luciferase activity was greatly reduced, suggesting that these binding elements play a functional role in the basal activation of the hTOP3 promoter [1].
  • Cellular studies of SMS patient lymphoblasts and their respective parental cell lines were undertaken to determine the consequences of haploinsufficiency of hTOP3 [6].
  • The present review first describes the different type I topoisomerases found in eukaryotic cells: nuclear topoisomerase I (top1), topoisomerase 3 (top3), mitochondrial topoisomerase I and viral topoisomerases I [7].
  • The TOP3 mRNA level in the testis increased slightly 14 days after birth and showed a marked increase in 17 days, times when the cells in pachytene phase begin to appear and increase in number [8].

Associations of TOP3A with chemical compounds

  • Here, we report that overexpression of a dominant-negative allele of TOP3, TOP3(Y356F), which lacks the catalytic (decatenation) activity of Top3, causes impaired S-phase progression and the persistence of abnormal DNA structures (X-shaped DNA molecules) after exposure to methylmethanesulfonate [5].

Other interactions of TOP3A

  • Most of the tumors displayed complex amplification profiles, with frequent involvement of marker D17S2041 in 17p12 and TOP3A in 17p11.2 and, in some cases, very high-level amplification of PMP22 and MAPK7 in 17p11 [9].
  • However, USF2 did not stimulate hTOP3 alpha promoter activity in Saos-2 cells [10].

Analytical, diagnostic and therapeutic context of TOP3A

  • Immunohistochemical analysis of the TOP3-treated xenografts confirmed that hypoxic cells underwent apoptosis and were removed after TOP3 treatment [11].


  1. Cloning and characterization of the 5'-flanking region for the human topoisomerase III gene. Kim, J.C., Yoon, J.B., Koo, H.S., Chung, I.K. J. Biol. Chem. (1998) [Pubmed]
  2. Overexpression of a truncated human topoisomerase III partially corrects multiple aspects of the ataxia-telangiectasia phenotype. Fritz, E., Elsea, S.H., Patel, P.I., Meyn, M.S. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  3. Human TOP3: a single-copy gene encoding DNA topoisomerase III. Hanai, R., Caron, P.R., Wang, J.C. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  4. Sgs1 regulates gene conversion tract lengths and crossovers independently of its helicase activity. Lo, Y.C., Paffett, K.S., Amit, O., Clikeman, J.A., Sterk, R., Brenneman, M.A., Nickoloff, J.A. Mol. Cell. Biol. (2006) [Pubmed]
  5. Top3 processes recombination intermediates and modulates checkpoint activity after DNA damage. Mankouri, H.W., Hickson, I.D. Mol. Biol. Cell (2006) [Pubmed]
  6. Gene for topoisomerase III maps within the Smith-Magenis syndrome critical region: analysis of cell-cycle distribution and radiation sensitivity. Elsea, S.H., Fritz, E., Schoener-Scott, R., Meyn, M.S., Patel, P.I. Am. J. Med. Genet. (1998) [Pubmed]
  7. Diversity of DNA topoisomerases I and inhibitors. Pommier, Y. Biochimie (1998) [Pubmed]
  8. Isolation of a cDNA encoding mouse DNA topoisomerase III which is highly expressed at the mRNA level in the testis. Seki, T., Seki, M., Katada, T., Enomoto, T. Biochim. Biophys. Acta (1998) [Pubmed]
  9. Amplification of 17p11.2 approximately p12, including PMP22, TOP3A, and MAPK7, in high-grade osteosarcoma. van Dartel, M., Cornelissen, P.W., Redeker, S., Tarkkanen, M., Knuutila, S., Hogendoorn, P.C., Westerveld, A., Gomes, I., Bras, J., Hulsebos, T.J. Cancer Genet. Cytogenet. (2002) [Pubmed]
  10. Cell type-dependent regulation of human DNA topoisomerase III alpha gene expression by upstream stimulatory factor 2. Han, S.Y., Kim, J.C., Suh, J.M., Chung, I.K. FEBS Lett. (2001) [Pubmed]
  11. Optical imaging of tumor hypoxia and evaluation of efficacy of a hypoxia-targeting drug in living animals. Harada, H., Kizaka-Kondoh, S., Hiraoka, M. Molecular imaging : official journal of the Society for Molecular Imaging. (2005) [Pubmed]
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