type i dna topoisomerases


Summary: DNA TOPOISOMERASES that catalyze ATP-independent breakage of one of the two strands of DNA, passage of the unbroken strand through the break, and rejoining of the broken strand. DNA Topoisomerases, Type I enzymes reduce the topological stress in the DNA structure by relaxing the superhelical turns and knotted rings in the DNA helix.

Top Publications

  1. Hackbarth J, Galvez Peralta M, Dai N, Loegering D, Peterson K, Meng X, et al. Mitotic phosphorylation stimulates DNA relaxation activity of human topoisomerase I. J Biol Chem. 2008;283:16711-22 pubmed publisher
    ..Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells. ..
  2. de la Loza M, Wellinger R. A novel approach for organelle-specific DNA damage targeting reveals different susceptibility of mitochondrial DNA to the anticancer drugs camptothecin and topotecan. Nucleic Acids Res. 2009;37:e26 pubmed publisher
    ..Our findings demonstrate that drug modifications can lead to organelle-specific DNA damage and thus opens new perspectives on the role of mitochondrial DNA-damage in cancer treatment. ..
  3. Chan K, North P, Hickson I. BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges. EMBO J. 2007;26:3397-409 pubmed
    ..We present a model for the action of BLM in ensuring complete sister chromatid decatenation in anaphase. ..
  4. Koster D, Palle K, Bot E, Bjornsti M, Dekker N. Antitumour drugs impede DNA uncoiling by topoisomerase I. Nature. 2007;448:213-7 pubmed
    ..This combination of single-molecule and in vivo data suggests a cytotoxic mechanism for camptothecins, in which the accumulation of positive supercoils ahead of the replication machinery induces potentially lethal DNA lesions. ..
  5. Mukherjee A, Sokunbi A, Grove A. DNA protection by histone-like protein HU from the hyperthermophilic eubacterium Thermotoga maritima. Nucleic Acids Res. 2008;36:3956-68 pubmed publisher
    ..We suggest that T. maritima HU serves an architectural function when associating with a single 35 bp site, but generates a very stable and compact aggregate at higher protein concentrations that organizes and protects the genomic DNA. ..
  6. Fiorani P, Tesauro C, Mancini G, Chillemi G, D Annessa I, Graziani G, et al. Evidence of the crucial role of the linker domain on the catalytic activity of human topoisomerase I by experimental and simulative characterization of the Lys681Ala mutant. Nucleic Acids Res. 2009;37:6849-58 pubmed publisher
    ..Taken together these results indicate the existence of a long range communication between the linker domain and the active site region and points out the crucial role of the linker in the modulation of the catalytic activity. ..
  7. Teicher B. Next generation topoisomerase I inhibitors: Rationale and biomarker strategies. Biochem Pharmacol. 2008;75:1262-71 pubmed
    ..A gene signature developed for topotecan sensitivity/resistance may have value in patient identification. Convergence of these efforts should result in clinically effective second generation TopoI inhibitors. ..
  8. Katyal S, El Khamisy S, Russell H, Li Y, Ju L, Caldecott K, et al. TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo. EMBO J. 2007;26:4720-31 pubmed
    ..These data indicate that TDP1 is required for neural homeostasis, and reveal a widespread requisite for TDP1 function in response to acutely elevated levels of Top1-associated DNA strand breaks. ..
  9. Miao Z, Player A, Shankavaram U, Wang Y, Zimonjic D, Lorenzi P, et al. Nonclassic functions of human topoisomerase I: genome-wide and pharmacologic analyses. Cancer Res. 2007;67:8752-61 pubmed
    ..The reported cell lines and approaches described in this article provide new tools to perform detailed functional analyses related to Top1 function. ..

More Information


  1. D Amaro A, Rossi M, Ciaramella M. Reverse gyrase: an unusual DNA manipulator of hyperthermophilic organisms. Ital J Biochem. 2007;56:103-9 pubmed
    ..We review here recent phylogenetic, biochemical and structural data on reverse gyrase and discuss the possible role of this enzyme in the biology of hyperthermophilic organisms. ..
  2. Gouveris P, Lazaris A, Papathomas T, Nonni A, Kyriakou V, Delladetsima J, et al. Topoisomerase I protein expression in primary colorectal cancer and recurrences after 5-FU-based adjuvant chemotherapy. J Cancer Res Clin Oncol. 2007;133:1011-5 pubmed
  3. Frøhlich R, Juul S, Nielsen M, Vinther M, Veigaard C, Hede M, et al. Identification of a minimal functional linker in human topoisomerase I by domain swapping with Cre recombinase. Biochemistry. 2008;47:7127-36 pubmed publisher
    ..In vitro characterization of the resulting chimeras, denoted Cropos, reveals that six amino acids from the Cre linker loop constitute the minimal length of a functional linker in human topoisomerase I. ..
  4. Sorokin E, Cheng B, Rathi S, Aedo S, Abrenica M, Tse Dinh Y. Inhibition of Mg2+ binding and DNA religation by bacterial topoisomerase I via introduction of an additional positive charge into the active site region. Nucleic Acids Res. 2008;36:4788-96 pubmed publisher
    ..This approach would be similar to the inhibition of divalent ion dependent strand transfer by HIV integrase in antiviral therapy...
  5. Lin C, Ban Y, Lyu Y, Liu L. Proteasome-dependent processing of topoisomerase I-DNA adducts into DNA double strand breaks at arrested replication forks. J Biol Chem. 2009;284:28084-92 pubmed publisher
  6. Hartung F, Suer S, Knoll A, Wurz Wildersinn R, Puchta H. Topoisomerase 3alpha and RMI1 suppress somatic crossovers and are essential for resolution of meiotic recombination intermediates in Arabidopsis thaliana. PLoS Genet. 2008;4:e1000285 pubmed publisher
  7. Lotito L, Russo A, Chillemi G, Bueno S, Cavalieri D, Capranico G. Global transcription regulation by DNA topoisomerase I in exponentially growing Saccharomyces cerevisiae cells: activation of telomere-proximal genes by TOP1 deletion. J Mol Biol. 2008;377:311-22 pubmed publisher
    ..As telomere-proximal regions are known to be enriched for stress-activated genes, our findings show that Top1p can optimize transcript levels for cell growth in exponentially growing cells under a synthetic medium with glucose. ..
  8. Schoeffler A, Berger J. DNA topoisomerases: harnessing and constraining energy to govern chromosome topology. Q Rev Biophys. 2008;41:41-101 pubmed publisher
  9. Cheng B, Sorokin E, Tse Dinh Y. Mutation adjacent to the active site tyrosine can enhance DNA cleavage and cell killing by the TOPRIM Gly to Ser mutant of bacterial topoisomerase I. Nucleic Acids Res. 2008;36:1017-25 pubmed
  10. Suski C, Marians K. Resolution of converging replication forks by RecQ and topoisomerase III. Mol Cell. 2008;30:779-89 pubmed publisher
    ..This resolution reaction is specific for the RecQ-topoisomerase III pair and is mediated by interaction of both of these enzymes with the single-stranded DNA-binding protein SSB. ..
  11. Hartung F, Suer S, Puchta H. Two closely related RecQ helicases have antagonistic roles in homologous recombination and DNA repair in Arabidopsis thaliana. Proc Natl Acad Sci U S A. 2007;104:18836-41 pubmed
    ..Moreover, they are strongly impaired in HR. Thus, AtRECQ4B is specifically required to promote but not to suppress crossovers, a role in which it differs from all eukaryotic RecQ homologues known. ..
  12. Bussen W, Raynard S, Busygina V, Singh A, Sung P. Holliday junction processing activity of the BLM-Topo IIIalpha-BLAP75 complex. J Biol Chem. 2007;282:31484-92 pubmed
  13. Perera A, Fertig N, Lucas M, Rodriguez Reyna T, Hu P, Steen V, et al. Clinical subsets, skin thickness progression rate, and serum antibody levels in systemic sclerosis patients with anti-topoisomerase I antibody. Arthritis Rheum. 2007;56:2740-6 pubmed
    ..Anti-topo I antibody levels parallel the MRSS at the first visit and the STPR. This information is important for managing physicians and researchers planning clinical trials involving patients with early dcSSc. ..
  14. Temime Smaali N, Guittat L, Wenner T, Bayart E, Douarre C, Gomez D, et al. Topoisomerase IIIalpha is required for normal proliferation and telomere stability in alternative lengthening of telomeres. EMBO J. 2008;27:1513-24 pubmed publisher
    ..We conclude that Topo IIIalpha is an important telomere-associated factor, essential for telomere maintenance and chromosome stability in ALT cells, and speculate on its potential mechanistic function. ..
  15. Hou M, Lu W, Lin H, Yuann J. Studies of sequence-specific DNA binding, DNA cleavage, and topoisomerase I inhibition by the dimeric chromomycin A3 complexed with Fe(II). Biochemistry. 2008;47:5493-502 pubmed publisher
    ..Our results provide significant evidence that the [(Chro)2-Fe(II)] complex could be promising in terms of its biological applications in the future. ..
  16. Goswami A, Qiu S, Dexheimer T, Ranganathan P, Burikhanov R, Pommier Y, et al. Par-4 binds to topoisomerase 1 and attenuates its DNA relaxation activity. Cancer Res. 2008;68:6190-8 pubmed publisher
    ..Collectively, our findings suggest that Par-4 serves as an intracellular repressor of TOP1 catalytic activity and regulates DNA topology to suppress cellular transformation. ..
  17. Jungblut S, Klostermeier D. Adenosine 5'-O-(3-thio)triphosphate (ATPgammaS) promotes positive supercoiling of DNA by T. maritima reverse gyrase. J Mol Biol. 2007;371:197-209 pubmed publisher
  18. Valenti A, Perugino G, D Amaro A, Cacace A, Napoli A, Rossi M, et al. Dissection of reverse gyrase activities: insight into the evolution of a thermostable molecular machine. Nucleic Acids Res. 2008;36:4587-97 pubmed publisher
    ..In addition, the two domains showed a striking reciprocal thermostabilization effect. ..
  19. Bouthier de La Tour C, Amrani L, Cossard R, Neuman K, Serre M, Duguet M. Mutational analysis of the helicase-like domain of Thermotoga maritima reverse gyrase. J Biol Chem. 2008;283:27395-402 pubmed publisher
    ..The zinc finger motif located at the N-terminal end of reverse gyrases was also mutated. Our results indicate that this motif plays an important role in DNA binding. ..
  20. Singh T, Ali A, Busygina V, Raynard S, Fan Q, Du C, et al. BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome. Genes Dev. 2008;22:2856-68 pubmed publisher
    ..Finally, BLAP18/RMI2 stimulates the dHJ resolution capability of the BTB complex. Together, these results establish BLAP18/RMI2 as an essential member of the BTB dHJ dissolvasome that is required for the maintenance of a stable genome. ..
  21. Mankouri H, Hickson I. The RecQ helicase-topoisomerase III-Rmi1 complex: a DNA structure-specific 'dissolvasome'?. Trends Biochem Sci. 2007;32:538-46 pubmed
  22. Tamby M, Bussone G, Mouthon L. Antitopoisomerase 1 antibodies in systemic sclerosis: how to improve the detection?. Ann N Y Acad Sci. 2007;1109:221-8 pubmed
    ..Thus, we may propose that a combination of the immunoblot using HEp-2 cells antigens and ELISA could be used for the detection of ATA. ..
  23. Perugino G, Valenti A, D Amaro A, Rossi M, Ciaramella M. Reverse gyrase and genome stability in hyperthermophilic organisms. Biochem Soc Trans. 2009;37:69-73 pubmed publisher
    ..In the present article, we review the latest progress on structure-function relationships of reverse gyrase, and discuss old and recent data linking reverse gyrase to DNA stability, protection and repair in hyperthermophilic organisms. ..
  24. Song J, Parker L, Hormozi L, Tanouye M. DNA topoisomerase I inhibitors ameliorate seizure-like behaviors and paralysis in a Drosophila model of epilepsy. Neuroscience. 2008;156:722-8 pubmed publisher
    ..Taken together, the results suggest that Top1 inhibitors may have the potential to be developed into effective anti-epileptic drugs, especially for brain tumor patients presenting with epilepsy. ..
  25. Xu D, Guo R, Sobeck A, Bachrati C, Yang J, Enomoto T, et al. RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability. Genes Dev. 2008;22:2843-55 pubmed publisher
    ..Our data suggest that multi-OB-fold complexes mediate two modes of BLM action: via RPA-mediated protein-DNA interaction, and via RMI-mediated protein-protein interactions. ..
  26. Liu Y, West S. More complexity to the Bloom's syndrome complex. Genes Dev. 2008;22:2737-42 pubmed publisher
    ..RMI2 may be a representative of a new family of OB-fold-containing proteins that are important for complex stabilization and checkpoint response. ..
  27. Chan A, Chang W, Chen L, Lee C, Chen C, Lin C, et al. Evodiamine stabilizes topoisomerase I-DNA cleavable complex to inhibit topoisomerase I activity. Molecules. 2009;14:1342-52 pubmed publisher
    ..2% in cells treated with 30 microM. The results suggest that EVO inhibits TopI by stabilizing the enzyme and DNA covalent complex. ..
  28. Basili S, Moro S. Novel camptothecin derivatives as topoisomerase I inhibitors. Expert Opin Ther Pat. 2009;19:555-74 pubmed publisher
    ..Structure-activity relationship studies suggest that substitutions at the 7-, 9- or 10-positions of most CPT derivatives enhance their antitumor activity, but at the 11- or 5-position usually lead to activity decrease. ..
  29. Zhang H, Pommier Y. Mitochondrial topoisomerase I sites in the regulatory D-loop region of mitochondrial DNA. Biochemistry. 2008;47:11196-203 pubmed publisher
    ..Moreover, we show that inhibition of Top1mt by camptothecin reduces the level of formation of the 7S DNA. These results suggest novel roles for Top1mt in regulating mtDNA replication. ..
  30. Sordet O, Larochelle S, Nicolas E, Stevens E, Zhang C, Shokat K, et al. Hyperphosphorylation of RNA polymerase II in response to topoisomerase I cleavage complexes and its association with transcription- and BRCA1-dependent degradation of topoisomerase I. J Mol Biol. 2008;381:540-9 pubmed publisher
    ..Finally, we show that transcription-induced degradation of Top1 is Brca1 dependent, suggesting a role for Brca1 in the repair or removal of transcription-blocking Top1-DNA cleavage complexes. ..
  31. Wethington S, Wright J, Herzog T. Key role of topoisomerase I inhibitors in the treatment of recurrent and refractory epithelial ovarian carcinoma. Expert Rev Anticancer Ther. 2008;8:819-31 pubmed publisher
    ..Conclusions include a discussion of future avenues of research and ongoing projects. ..
  32. Courapied S, Sellier H, de Carné Trécesson S, Vigneron A, Bernard A, Gamelin E, et al. The cdk5 kinase regulates the STAT3 transcription factor to prevent DNA damage upon topoisomerase I inhibition. J Biol Chem. 2010;285:26765-78 pubmed publisher
    ..We therefore propose that the cdk5-STAT3 oncogenic pathway plays an important role in the expression of DNA repair genes and that these proteins could be used as predictive markers of tumors that will fail to respond to chemotherapy. ..
  33. Laco G, Pommier Y. Role of a tryptophan anchor in human topoisomerase I structure, function and inhibition. Biochem J. 2008;411:523-30 pubmed publisher
    ..The results indicated that the tryptophan anchor stabilized the N-terminus of the functional domain and prevented the loss of Top1 structure and function. ..
  34. Takagi K, Dexheimer T, Redon C, Sordet O, Agama K, Lavielle G, et al. Novel E-ring camptothecin keto analogues (S38809 and S39625) are stable, potent, and selective topoisomerase I inhibitors without being substrates of drug efflux transporters. Mol Cancer Ther. 2007;6:3229-38 pubmed
    ..Histone gamma-H2AX could be used as a biomarker for the upcoming clinical trials of S39625. ..
  35. Chen C, Brill S. Binding and activation of DNA topoisomerase III by the Rmi1 subunit. J Biol Chem. 2007;282:28971-9 pubmed
    ..These results demonstrate that Top3-Rmi1 functions as a complex and suggest that Rmi1 stimulates Top3 by promoting its interaction with ssDNA. ..
  36. Szklarczyk O, Staron K, Cieplak M. Native state dynamics and mechanical properties of human topoisomerase I within a structure-based coarse-grained model. Proteins. 2009;77:420-31 pubmed publisher
    ..We find supporting evidence for the hypothesis that the C-terminal domain acquires an ordered structure upon binding with the core enzyme even though it forms a molten globule when in isolation. ..
  37. Siu F, Che C. Persistence of camptothecin analog-topoisomerase I-DNA ternary complexes: a molecular dynamics study. J Am Chem Soc. 2008;130:17928-37 pubmed publisher
  38. Vigneron A, Gamelin E, Coqueret O. The EGFR-STAT3 oncogenic pathway up-regulates the Eme1 endonuclease to reduce DNA damage after topoisomerase I inhibition. Cancer Res. 2008;68:815-25 pubmed publisher
    ..We therefore propose that the benefit of anti-EGFR therapy relies on an increase of DNA damage generated by topoisomerase I inhibition. ..
  39. Miao Z, Agama K, Sordet O, Povirk L, Kohn K, Pommier Y. Hereditary ataxia SCAN1 cells are defective for the repair of transcription-dependent topoisomerase I cleavage complexes. DNA Repair (Amst). 2006;5:1489-94 pubmed
  40. Nagarajan M, Morrell A, Ioanoviciu A, Antony S, Kohlhagen G, Agama K, et al. Synthesis and evaluation of indenoisoquinoline topoisomerase I inhibitors substituted with nitrogen heterocycles. J Med Chem. 2006;49:6283-9 pubmed
  41. Minkah N, Hwang Y, Perry K, Van Duyne G, Hendrickson R, Lefkowitz E, et al. Variola virus topoisomerase: DNA cleavage specificity and distribution of sites in Poxvirus genomes. Virology. 2007;365:60-9 pubmed
    ..These data define the full variola virus topoisomerase recognition site and provide a new window on topoisomerase function in vivo...
  42. Abdurashidova G, Radulescu S, Sandoval O, Zahariev S, Danailov M, Demidovich A, et al. Functional interactions of DNA topoisomerases with a human replication origin. EMBO J. 2007;26:998-1009 pubmed
    ..Inhibition of topoisomerase I activity abolishes origin firing. Thus, the two topoisomerases are closely associated with the replicative complexes, and DNA topology plays an essential functional role in origin activation. ..
  43. Hsieh T, Plank J. Reverse gyrase functions as a DNA renaturase: annealing of complementary single-stranded circles and positive supercoiling of a bubble substrate. J Biol Chem. 2006;281:5640-7 pubmed
    ..These biochemical activities also suggest that reverse gyrase can have an important biological function in sensing and eliminating unpaired regions in the genome of a hyperthermophilic organism. ..
  44. Nadal M. Reverse gyrase: an insight into the role of DNA-topoisomerases. Biochimie. 2007;89:447-55 pubmed
    ..These data give us a new insight in the cellular role of reverse gyrase. Moreover, it has been proposed that reverse gyrase has been implicated in genome stability. ..
  45. Raynard S, Bussen W, Sung P. A double Holliday junction dissolvasome comprising BLM, topoisomerase IIIalpha, and BLAP75. J Biol Chem. 2006;281:13861-4 pubmed
    ..This function of the BLM-Topo IIIalpha-BLAP75 dissolvasome is likely indispensable for genome maintenance and cancer avoidance. ..
  46. Capranico G, Ferri F, Fogli M, Russo A, Lotito L, Baranello L. The effects of camptothecin on RNA polymerase II transcription: roles of DNA topoisomerase I. Biochimie. 2007;89:482-9 pubmed
    ..Here, we will briefly review relevant investigations on topoisomerase I involvement in different stages of transcription, discussing both enzyme functions and drug effects on molecular processes. ..
  47. Perry K, Hwang Y, Bushman F, Van Duyne G. Structural basis for specificity in the poxvirus topoisomerase. Mol Cell. 2006;23:343-54 pubmed publisher
    ..The topoisomerase-DNA complex structures also provide a three-dimensional framework that may facilitate the rational design of therapeutic agents to treat poxvirus infections...
  48. Seki M, Nakagawa T, Seki T, Kato G, Tada S, Takahashi Y, et al. Bloom helicase and DNA topoisomerase IIIalpha are involved in the dissolution of sister chromatids. Mol Cell Biol. 2006;26:6299-307 pubmed
    ..Taken together with the biochemical properties of BLM and Top3alpha, these data indicate that BLM and Top3alpha execute the dissolution of sister chromatids. ..
  49. Zhang H, Meng L, Pommier Y. Mitochondrial topoisomerases and alternative splicing of the human TOP1mt gene. Biochimie. 2007;89:474-81 pubmed
    ..It also includes new data showing alternative splice variants of human TOP1mt. ..
  50. Kaufmann S, Karp J, Letendre L, Kottke T, Safgren S, Greer J, et al. Phase I and pharmacologic study of infusional topotecan and Carboplatin in relapsed and refractory acute leukemia. Clin Cancer Res. 2005;11:6641-9 pubmed
    ..The complete remission rate in a heavily pretreated population was 16% (33% at the highest three dose levels). Responses seem to correlate with low pretreatment blast cell Bcl-2 expression. ..
  51. Nagarajan R, Kwon K, Nawrot B, Stec W, Stivers J. Catalytic phosphoryl interactions of topoisomerase IB. Biochemistry. 2005;44:11476-85 pubmed
    ..A key finding is the central role of Arg130, which forms electrostatic interactions with both nonbridging oxygens and the 5'-leaving group. ..
  52. Pommier Y. Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer. 2006;6:789-802 pubmed
  53. Tse Dinh Y. Exploring DNA topoisomerases as targets of novel therapeutic agents in the treatment of infectious diseases. Infect Disord Drug Targets. 2007;7:3-9 pubmed
    ..These new developments of DNA topoisomerases as targets of novel therapeutic agents being reviewed here represent excellent opportunities for drug discovery in the treatment of infectious diseases. ..
  54. Brochier Armanet C, Forterre P. Widespread distribution of archaeal reverse gyrase in thermophilic bacteria suggests a complex history of vertical inheritance and lateral gene transfers. Archaea. 2007;2:83-93 pubmed
    ..However, it also questions the role of this enzyme in thermophilic bacteria and the selective advantage its presence could provide. ..
  55. Wu L, Bachrati C, Ou J, Xu C, Yin J, Chang M, et al. BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates. Proc Natl Acad Sci U S A. 2006;103:4068-73 pubmed
    ..Implications of the conserved ability of type IA topoisomerases to catalyze dissolution and how the evolution of factors such as BLAP75/RMI1 might confer specificity on the execution of this process are discussed. ..
  56. Davies D, Mushtaq A, Interthal H, Champoux J, Hol W. The structure of the transition state of the heterodimeric topoisomerase I of Leishmania donovani as a vanadate complex with nicked DNA. J Mol Biol. 2006;357:1202-10 pubmed
    ..This structure fills a critical gap in the existing ensemble of topoisomerase I structures and provides crucial insights into the catalytic mechanism...
  57. Ikegami T, Matsuzaki Y, Al Rashid M, Ceryak S, Zhang Y, Bouscarel B. Enhancement of DNA topoisomerase I inhibitor-induced apoptosis by ursodeoxycholic acid. Mol Cancer Ther. 2006;5:68-79 pubmed
    ..However, the use of this bile acid as an enhancer in antitumor chemotherapy should be further evaluated clinically. ..
  58. Cheng B, Shukla S, Vasunilashorn S, Mukhopadhyay S, Tse Dinh Y. Bacterial cell killing mediated by topoisomerase I DNA cleavage activity. J Biol Chem. 2005;280:38489-95 pubmed
    ..Small molecules that induce similar perturbation in the enzyme-DNA complex should be candidates as leads for novel antibacterial agents. ..
  59. Balaña Fouce R, Redondo C, Pérez Pertejo Y, Díaz González R, Reguera R. Targeting atypical trypanosomatid DNA topoisomerase I. Drug Discov Today. 2006;11:733-40 pubmed
    ..The substantial differences in homology between trypanosome and leishmania DNA topoisomerase IB compared with the human form provides a new lead in the study of the structural determinants that can be targeted. ..
  60. Meyer O, Fertig N, Lucas M, Somogyi N, Medsger T. Disease subsets, antinuclear antibody profile, and clinical features in 127 French and 247 US adult patients with systemic sclerosis. J Rheumatol. 2007;34:104-9 pubmed
    ..There are disease classification and SSc-related serum autoantibody differences between French and American patients with SSc. These differences help to explain variations in clinical features reported from different geographic regions. ..
  61. Tsai H, Huang W, Li T, Tsai Y, Wu K, Tseng S, et al. Involvement of topoisomerase III in telomere-telomere recombination. J Biol Chem. 2006;281:13717-23 pubmed
    ..Altogether, the present results suggest a potential role for hTOP3alpha in dissociating telomeric structures in telomerase-deficient cells, providing therapeutic implications in human tumors. ..