Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 6 March 1998:
Vol. 279. no. 5356, pp. 1534 - 1541
DOI: 10.1126/science.279.5356.1534
Prev | Table of Contents | Next

Reports

A Model for the Mechanism of Human Topoisomerase I

Lance Stewart, *dagger Matthew R. Redinbo, * Xiayang Qiu, ddagger Wim G. J. Hol, James J. Champoux §

The three-dimensional structure of a 70-kilodalton amino terminally truncated form of human topoisomerase I in complex with a 22-base pair duplex oligonucleotide, determined to a resolution of 2.8 angstroms, reveals all of the structural elements of the enzyme that contact DNA. The linker region that connects the central core of the enzyme to the carboxyl-terminal domain assumes a coiled-coil configuration and protrudes away from the remainder of the enzyme. The positively charged DNA-proximal surface of the linker makes only a few contacts with the DNA downstream of the cleavage site. In combination with the crystal structures of the reconstituted human topoisomerase I before and after DNA cleavage, this information suggests which amino acid residues are involved in catalyzing phosphodiester bond breakage and religation. The structures also lead to the proposal that the topoisomerization step occurs by a mechanism termed "controlled rotation."

L. Stewart, M. R. Redinbo, X. Qiu, Biomolecular Structure Center and Department of Biological Structure, School of Medicine, University of Washington, Seattle, WA 98195-7742, USA.
W. G. J. Hol, Departments of Biological Structure and Biochemistry, Biomolecular Structure Center, and Howard Hughes Medical Institute, School of Medicine, University of Washington, Seattle, WA 98195-7742, USA.
J. J. Champoux, Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195-7242, USA.
*   These authors contributed equally to this work.

dagger    Present address: Emerald BioStructures, Incorporated, 7865 Northeast Day Road West, Bainbridge Island, WA 98110, USA. E-mail: emerald_biostructures{at}rocketmail.com

ddagger    Present address: Department of Structural Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.

§   To whom correspondence should be addressed: E-mail: champoux{at}u.washington.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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.
P. Fiorani, C. Tesauro, G. Mancini, G. Chillemi, I. D'A;nnessa, G. Graziani, L. Tentori, A. Muzi, and A. Desideri (2009)
Nucleic Acids Res. 37, 6849-6858
   Abstract »    Full Text »    PDF »
A novel approach for organelle-specific DNA damage targeting reveals different susceptibility of mitochondrial DNA to the anticancer drugs camptothecin and topotecan.
M. C. D. de la Loza and R. E. Wellinger (2009)
Nucleic Acids Res. 37, e26
   Abstract »    Full Text »    PDF »
Structural studies of type I topoisomerases.
N. M. Baker, R. Rajan, and A. Mondragon (2009)
Nucleic Acids Res. 37, 693-701
   Abstract »    Full Text »    PDF »
Disulfide Cross-links Reveal Conserved Features of DNA Topoisomerase I Architecture and a Role for the N Terminus in Clamp Closure.
K. Palle, L. Pattarello, M. van der Merwe, C. Losasso, P. Benedetti, and M.-A. Bjornsti (2008)
J. Biol. Chem. 283, 27767-27775
   Abstract »    Full Text »    PDF »
Thr729 in human topoisomerase I modulates anti-cancer drug resistance by altering protein domain communications as suggested by molecular dynamics simulations.
G. Chillemi, I. D'Annessa, P. Fiorani, C. Losasso, P. Benedetti, and A. Desideri (2008)
Nucleic Acids Res. 36, 5645-5651
   Abstract »    Full Text »    PDF »
A single mutation in the 729 residue modulates human DNA topoisomerase IB DNA binding and drug resistance.
C. Losasso, E. Cretaio, P. Fiorani, I. D'Annessa, G. Chillemi, and P. Benedetti (2008)
Nucleic Acids Res. 36, 5635-5644
   Abstract »    Full Text »    PDF »
From the Cover: Mutations in topoisomerase I as a self-resistance mechanism coevolved with the production of the anticancer alkaloid camptothecin in plants.
S. Sirikantaramas, M. Yamazaki, and K. Saito (2008)
PNAS 105, 6782-6786
   Abstract »    Full Text »    PDF »
Single-molecule observations of topotecan-mediated TopIB activity at a unique DNA sequence.
D. A. Koster, F. Czerwinski, L. Halby, A. Crut, P. Vekhoff, K. Palle, P. B. Arimondo, and N. H. Dekker (2008)
Nucleic Acids Res. 36, 2301-2310
   Abstract »    Full Text »    PDF »
Mutation of Gly721 Alters DNA Topoisomerase I Active Site Architecture and Sensitivity to Camptothecin.
M. van der Merwe and M.-A. Bjornsti (2008)
J. Biol. Chem. 283, 3305-3315
   Abstract »    Full Text »    PDF »
Tryptophane-205 of human topoisomerase I is essential for camptothecin inhibition of negative but not positive supercoil removal.
R. F. Frohlich, C. Veigaard, F. F. Andersen, A. K. McClendon, A. C. Gentry, A. H. Andersen, N. Osheroff, T. Stevnsner, and B. R. Knudsen (2007)
Nucleic Acids Res. 35, 6170-6180
   Abstract »    Full Text »    PDF »
Topoisomerase V relaxes supercoiled DNA by a constrained swiveling mechanism.
B. Taneja, B. Schnurr, A. Slesarev, J. F. Marko, and A. Mondragon (2007)
PNAS 104, 14670-14675
   Abstract »    Full Text »    PDF »
The open state of human topoisomerase I as probed by molecular dynamics simulation.
G. Chillemi, A. Bruselles, P. Fiorani, S. Bueno, and A. Desideri (2007)
Nucleic Acids Res. 35, 3032-3038
   Abstract »    Full Text »    PDF »
Inhibition of Topoisomerase I Cleavage Activity by Thiol-reactive Compounds: IMPORTANCE OF VICINAL CYSTEINES 504 AND 505.
D. Montaudon, K. Palle, L. P. Rivory, J. Robert, C. Douat-Casassus, S. Quideau, M.-A. Bjornsti, and P. Pourquier (2007)
J. Biol. Chem. 282, 14403-14412
   Abstract »    Full Text »    PDF »
Alterations in Linker Flexibility Suppress DNA Topoisomerase I Mutant-induced Cell Lethality.
C. Losasso, E. Cretaio, K. Palle, L. Pattarello, M.-A. Bjornsti, and P. Benedetti (2007)
J. Biol. Chem. 282, 9855-9864
   Abstract »    Full Text »    PDF »
NKX3.1 Homeodomain Protein Binds to Topoisomerase I and Enhances Its Activity.
C. Bowen, A. Stuart, J.-H. Ju, J. Tuan, J. Blonder, T. P. Conrads, T. D. Veenstra, and E. P. Gelmann (2007)
Cancer Res. 67, 455-464
   Abstract »    Full Text »    PDF »
The different cleavage DNA sequence specificity explains the camptothecin resistance of the human topoisomerase I Glu418Lys mutant.
P. Fiorani, G. Chillemi, C. Losasso, S. Castelli, and A. Desideri (2006)
Nucleic Acids Res. 34, 5093-5100
   Abstract »    Full Text »    PDF »
Evolution of variants of yeast site-specific recombinase Flp that utilize native genomic sequences as recombination target sites.
S. Bolusani, C.-H. Ma, A. Paek, J. H. Konieczka, M. Jayaram, and Y. Voziyanov (2006)
Nucleic Acids Res. 34, 5259-5269
   Abstract »    Full Text »    PDF »
Reverse Gyrase Functions as a DNA Renaturase: ANNEALING OF COMPLEMENTARY SINGLE-STRANDED CIRCLES AND POSITIVE SUPERCOILING OF A BUBBLE SUBSTRATE.
T.-s. Hsieh and J. L. Plank (2006)
J. Biol. Chem. 281, 5640-5647
   Abstract »    Full Text »    PDF »
Novel missense mutation of the DNA topoisomerase I gene in SN-38-resistant DLD-1 cells..
Y. Arakawa, H. Suzuki, S. Saito, and H. Yamada (2006)
Mol. Cancer Ther. 5, 502-508
   Abstract »    Full Text »    PDF »
A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex..
C. Marchand, S. Antony, K. W. Kohn, M. Cushman, A. Ioanoviciu, B. L. Staker, A. B. Burgin, L. Stewart, and Y. Pommier (2006)
Mol. Cancer Ther. 5, 287-295
   Abstract »    Full Text »    PDF »
Rotation of DNA around intact strand in human topoisomerase I implies distinct mechanisms for positive and negative supercoil relaxation.
L. Sari and I. Andricioaei (2005)
Nucleic Acids Res. 33, 6621-6634
   Abstract »    Full Text »    PDF »
Human Tdp1 Cleaves a Broad Spectrum of Substrates, Including Phosphoamide Linkages.
H. Interthal, H. J. Chen, and J. J. Champoux (2005)
J. Biol. Chem. 280, 36518-36528
   Abstract »    Full Text »    PDF »
Effect on DNA relaxation of the single Thr718Ala mutation in human topoisomerase I: a functional and molecular dynamics study.
G. Chillemi, P. Fiorani, S. Castelli, A. Bruselles, P. Benedetti, and A. Desideri (2005)
Nucleic Acids Res. 33, 3339-3350
   Abstract »    Full Text »    PDF »
Nucleotide- and Stoichiometry-dependent DNA Supercoiling by Reverse Gyrase.
T.-s. Hsieh and C. Capp (2005)
J. Biol. Chem. 280, 20467-20475
   Abstract »    Full Text »    PDF »
Topoisomerase I Amino Acid Substitutions, Gly185Arg and Asp325Glu, Confer Camptothecin Resistance in Leishmania donovani.
J.-F. Marquis, I. Hardy, and M. Olivier (2005)
Antimicrob. Agents Chemother. 49, 1441-1446
   Abstract »    Full Text »    PDF »
Substitution of Conserved Residues within the Active Site Alters the Cleavage Religation Equilibrium of DNA Topoisomerase I.
W. C. Colley, M. van der Merwe, J. R. Vance, A. B. Burgin Jr., and M.-A. Bjornsti (2004)
J. Biol. Chem. 279, 54069-54078
   Abstract »    Full Text »    PDF »
Phosphorylation of DNA Topoisomerase I by the c-Abl Tyrosine Kinase Confers Camptothecin Sensitivity.
D. Yu, E. Khan, M. A. Khaleque, J. Lee, G. Laco, G. Kohlhagen, S. Kharbanda, Y.-C. Cheng, Y. Pommier, and A. Bharti (2004)
J. Biol. Chem. 279, 51851-51861
   Abstract »    Full Text »    PDF »
Pyridoxal 5'-phosphate inactivates DNA topoisomerase IB by modifying the lysine general acid.
J. J. Vermeersch, S. Christmann-Franck, L. V. Karabashyan, S. Fermandjian, G. Mirambeau, and P. A. Der Garabedian (2004)
Nucleic Acids Res. 32, 5649-5657
   Abstract »    Full Text »    PDF »
Position- and orientation-specific enhancement of topoisomerase I cleavage complexes by triplex DNA structures.
S. Antony, P. B. Arimondo, J.-S. Sun, and Y. Pommier (2004)
Nucleic Acids Res. 32, 5163-5173
   Abstract »    Full Text »    PDF »
NUP98-Topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation.
R. M. Gurevich, P. D. Aplan, and R. K. Humphries (2004)
Blood 104, 1127-1136
   Abstract »    Full Text »    PDF »
The Deubiquitinating Enzyme Doa4p Protects Cells from DNA Topoisomerase I Poisons.
P. Fiorani, R. J. D. Reid, A. Schepis, H. R. Jacquiau, H. Guo, P. Thimmaiah, P. Benedetti, and M.-A. Bjornsti (2004)
J. Biol. Chem. 279, 21271-21281
   Abstract »    Full Text »    PDF »
Poly(ADP-ribose) Reactivates Stalled DNA Topoisomerase I and Induces DNA Strand Break Resealing.
M. Malanga and F. R. Althaus (2004)
J. Biol. Chem. 279, 5244-5248
   Abstract »    Full Text »    PDF »
Reversible Inhibitors of {lambda} Integrase-mediated Recombination Efficiently Trap Holliday Junction Intermediates and Form the Basis of a Novel Assay for Junction Resolution.
J. L. Boldt, C. Pinilla, and A. M. Segall (2004)
J. Biol. Chem. 279, 3472-3483
   Abstract »    Full Text »    PDF »
The Role of Lysine 532 in the Catalytic Mechanism of Human Topoisomerase I.
H. Interthal, P. M. Quigley, W. G. J. Hol, and J. J. Champoux (2004)
J. Biol. Chem. 279, 2984-2992
   Abstract »    Full Text »    PDF »
Residues 190-210 of human topoisomerase I are required for enzyme activity in vivo but not in vitro.
M. O. Christensen, H. U. Barthelmes, F. Boege, and C. Mielke (2003)
Nucleic Acids Res. 31, 7255-7263
   Abstract »    Full Text »    PDF »
Locking the DNA topoisomerase I protein clamp inhibits DNA rotation and induces cell lethality.
M. H. Woo, C. Losasso, H. Guo, L. Pattarello, P. Benedetti, and M.-A. Bjornsti (2003)
PNAS 100, 13767-13772
   Abstract »    Full Text »    PDF »
Differential Induction of Topoisomerase I-DNA Cleavage Complexes by the Indenoisoquinoline MJ-III-65 (NSC 706744) and Camptothecin: Base Sequence Analysis and Activity against Camptothecin- Resistant Topoisomerases I.
S. Antony, M. Jayaraman, G. Laco, G. Kohlhagen, K. W. Kohn, M. Cushman, and Y. Pommier (2003)
Cancer Res. 63, 7428-7435
   Abstract »    Full Text »    PDF »
Single Mutation in the Linker Domain Confers Protein Flexibility and Camptothecin Resistance to Human Topoisomerase I.
P. Fiorani, A. Bruselles, M. Falconi, G. Chillemi, A. Desideri, and P. Benedetti (2003)
J. Biol. Chem. 278, 43268-43275
   Abstract »    Full Text »    PDF »
Site-specific DNA Transesterification by Vaccinia Topoisomerase: EFFECTS OF BENZO[{alpha}]PYRENE-dA, 8-OXOGUANINE, 8-OXOADENINE, AND 2-AMINOPURINE MODIFICATIONS.
L. Yakovleva, L. Tian, J. M. Sayer, G. P. Kalena, H. Kroth, D. M. Jerina, and S. Shuman (2003)
J. Biol. Chem. 278, 42170-42177
   Abstract »    Full Text »    PDF »
The Cap Region of Topoisomerase I Binds to Sites near Both Ends of Simian Virus 40 T Antigen.
R. Roy, P. Trowbridge, Z. Yang, J. J. Champoux, and D. T. Simmons (2003)
J. Virol. 77, 9809-9816
   Abstract »    Full Text »    PDF »
Spatial organization of topoisomerase I-mediated DNA cleavage induced by camptothecin-oligonucleotide conjugates.
P. B. Arimondo, S. Angenault, L. Halby, A. Boutorine, F. Schmidt, C. Monneret, T. Garestier, J.-S. Sun, C. Bailly, and C. Helene (2003)
Nucleic Acids Res. 31, 4031-4040
   Abstract »    Full Text »    PDF »
The Role of the Conserved Trp330 in Flp-mediated Recombination: FUNCTIONAL AND STRUCTURAL ANALYSIS.
Y. Chen and P. A. Rice (2003)
J. Biol. Chem. 278, 24800-24807
   Abstract »    Full Text »    PDF »
Phosphorylation of Histone H2AX and Activation of Mre11, Rad50, and Nbs1 in Response to Replication-dependent DNA Double-strand Breaks Induced by Mammalian DNA Topoisomerase I Cleavage Complexes.
T. Furuta, H. Takemura, Z.-Y. Liao, G. J. Aune, C. Redon, O. A. Sedelnikova, D. R. Pilch, E. P. Rogakou, A. Celeste, H. T. Chen, et al. (2003)
J. Biol. Chem. 278, 20303-20312
   Abstract »    Full Text »    PDF »
DNA relaxation by human topoisomerase I occurs in the closed clamp conformation of the protein.
J. F. Carey, S. J. Schultz, L. Sisson, T. G. Fazzio, and J. J. Champoux (2003)
PNAS 100, 5640-5645
   Abstract »    Full Text »    PDF »
Structural Impact of the Leukemia Drug 1-beta -D-Arabinofuranosylcytosine (Ara-C) on the Covalent Human Topoisomerase I-DNA Complex.
J. E. Chrencik, A. B. Burgin, Y. Pommier, L. Stewart, and M. R. Redinbo (2003)
J. Biol. Chem. 278, 12461-12466
   Abstract »    Full Text »    PDF »
Protein concerted motions in the DNA-human topoisomerase I complex.
G. Chillemi, P. Fiorani, P. Benedetti, and A. Desideri (2003)
Nucleic Acids Res. 31, 1525-1535
   Abstract »    Full Text »    PDF »
Irinotecan: mechanisms of tumor resistance and novel strategies for modulating its activity.
Y. Xu and M. A. Villalona-Calero (2002)
Ann. Onc. 13, 1841-1851
   Abstract »    Full Text »    PDF »
Type IA DNA topoisomerases: Strictly one step at a time.
J. J. Champoux (2002)
PNAS 99, 11998-12000
   Full Text »    PDF »
8-Oxoguanine rearranges the active site of human topoisomerase I.
D.-T. T. Lesher, Y. Pommier, L. Stewart, and M. R. Redinbo (2002)
PNAS 99, 12102-12107
   Abstract »    Full Text »    PDF »
From the Cover: The mechanism of type IA topoisomerases.
N. H. Dekker, V. V. Rybenkov, M. Duguet, N. J. Crisona, N. R. Cozzarelli, D. Bensimon, and V. Croquette (2002)
PNAS 99, 12126-12131
   Abstract »    Full Text »    PDF »
Reconstitution of Enzymatic Activity by the Association of the Cap and Catalytic Domains of Human Topoisomerase I.
Z. Yang and J. J. Champoux (2002)
J. Biol. Chem. 277, 30815-30823
   Abstract »    Full Text »    PDF »
Molecular Characterization of Recombinant Pneumocystis carinii Topoisomerase I: Differential Interactions with Human Topoisomerase I Poisons and Pentamidine.
R. T. Van Dross and M. M. Sanders (2002)
Antimicrob. Agents Chemother. 46, 2145-2154
   Abstract »    Full Text »    PDF »
An insight into the active site of a type I DNA topoisomerase from the kinetoplastid protozoan Leishmania donovani.
A. Das, C. Mandal, A. Dasgupta, T. Sengupta, and H. K. Majumder (2002)
Nucleic Acids Res. 30, 794-802
   Abstract »    Full Text »    PDF »
Active Site Mutations in DNA Topoisomerase I Distinguish the Cytotoxic Activities of Camptothecin and the Indolocarbazole, Rebeccamycin.
M. H. Woo, J. R. Vance, A. R. O. Marcos, C. Bailly, and M.-A. Bjornsti (2002)
J. Biol. Chem. 277, 3813-3822
   Abstract »    Full Text »    PDF »
Recurrent coiled-coil motifs in NUP98 fusion partners provide a clue to leukemogenesis.
D. J. Hussey and A. Dobrovic (2002)
Blood 99, 1097
   Full Text »    PDF »
Design and Optimization of Camptothecin Conjugates of Triple Helix-forming Oligonucleotides for Sequence-specific DNA Cleavage by Topoisomerase I.
P. B. Arimondo, A. Boutorine, B. Baldeyrou, C. Bailly, M. Kuwahara, S. M. Hecht, J.-S. Sun, T. Garestier, and C. Helene (2002)
J. Biol. Chem. 277, 3132-3140
   Abstract »    Full Text »    PDF »
Hyperthermophilic Topoisomerase I from Thermotoga maritima. A VERY EFFICIENT ENZYME THAT FUNCTIONS INDEPENDENTLY OF ZINC BINDING.
T. Viard, V. Lamour, M. Duguet, and C. Bouthier de la Tour (2001)
J. Biol. Chem. 276, 46495-46503
   Abstract »    Full Text »    PDF »
Molecular characterization of the Rep protein of the blackgram isolate of Indian mungbean yellow mosaic virus.
V. Pant, D. Gupta, N. R. Choudhury, V. G. Malathi, A. Varma, and S. K. Mukherjee (2001)
J. Gen. Virol. 82, 2559-2567
   Abstract »    Full Text »    PDF »
A human topoisomerase I cleavage complex is recognized by an additional human topisomerase I molecule in vitro.
K. Soe, G. Dianov, H.-P. Nasheuer, V. A. Bohr, F. Grosse, and T. Stevnsner (2001)
Nucleic Acids Res. 29, 3195-3203
   Abstract »    Full Text »    PDF »
Hoechst 33342-Induced Apoptosis is Associated with Decreased Immunoreactive Topoisomerase I and Topoisomerase I-DNA Complex Formation.
X. Zhang and F. Kiechle (2001)
Ann. Clin. Lab. Sci. 31, 187-198
   Abstract »    Full Text »    PDF »
Irinotecan in the Treatment of Colorectal Cancer: Clinical Overview.
U. Vanhoefer, A. Harstrick, W. Achterrath, S. Cao, S. Seeber, and Y. M. Rustum (2001)
J. Clin. Oncol. 19, 1501-1518
   Abstract »    Full Text »    PDF »
A nicked duplex decamer DNA with a PEG6 tether.
L. Kozerski, A. P. Mazurek, R. Kawecki, W. Bocian, P. Krajewski, E. Bednarek, J. Sitkowski, M. P. Williamson, A. J. G. Moir, and P. E. Hansen (2001)
Nucleic Acids Res. 29, 1132-1143
   Abstract »    Full Text »    PDF »
Characterization of a Novel Topoisomerase I Mutation from a Camptothecin-resistant Human Prostate Cancer Cell Line.
Y. Urasaki, G. S. Laco, P. Pourquier, Y. Takebayashi, G. Kohlhagen, C. Gioffre, H. Zhang, D. Chatterjee, P. Pantazis, and Y. Pommier (2001)
Cancer Res. 61, 1964-1969
   Abstract »    Full Text »
Use of Camptothecin-resistant Mammalian Cell Lines to Evaluate the Role of Topoisomerase I in the Antiproliferative Activity of the Indolocarbazole, NB-506, and Its Topoisomerase I Binding Site.
Y. Urasaki, G. Laco, Y. Takebayashi, C. Bailly, G. Kohlhagen, and Y. Pommier (2001)
Cancer Res. 61, 504-508
   Abstract »    Full Text »
Position-specific trapping of topoisomerase I-DNA cleavage complexes by intercalated benzo[a]- pyrene diol epoxide adducts at the 6-amino group of adenine.
Y. Pommier, G. S. Laco, G. Kohlhagen, J. M. Sayer, H. Kroth, and D. M. Jerina (2000)
PNAS
   Abstract »    Full Text »
p53 Dependence of Topoisomerase I Recruitment in Vivo.
Y. Mao, S. Okada, L.-S. Chang, and M. T. Muller (2000)
Cancer Res. 60, 4538-4543
   Abstract »    Full Text »
Conversion of Topoisomerase I Cleavage Complexes on the Leading Strand of Ribosomal DNA into 5'-Phosphorylated DNA Double-Strand Breaks by Replication Runoff.
D. Strumberg, A. A. Pilon, M. Smith, R. Hickey, L. Malkas, and Y. Pommier (2000)
Mol. Cell. Biol. 20, 3977-3987
   Abstract »    Full Text »
Substitutions of Asn-726 in the Active Site of Yeast DNA Topoisomerase I Define Novel Mechanisms of Stabilizing the Covalent Enzyme-DNA Intermediate.
J. Fertala, J. R. Vance, P. Pourquier, Y. Pommier, and M.-A. Bjornsti (2000)
J. Biol. Chem. 275, 15246-15253
   Abstract »    Full Text »    PDF »
DNA strand transfer catalyzed by vaccinia topoisomerase: ligation of DNAs containing a 3' mononucleotide overhang.
C. Cheng and S. Shuman (2000)
Nucleic Acids Res. 28, 1893-1898
   Abstract »    Full Text »    PDF »
Determination of the recognition sequence of Mycobacterium smegmatis topoisomerase I on mycobacterial genomic sequences.
D. Sikder and V. Nagaraja (2000)
Nucleic Acids Res. 28, 1830-1837
   Abstract »    Full Text »    PDF »
CBFA1 and Topoisomerase I mRNA Levels Decline During Cellular Aging of Human Trabecular Osteoblasts.
M. Christiansen, M. Kveiborg, M. Kassem, B. F. C. Clark, and S. I. S. Rattan (2000)
J. Gerontol. A Biol. Sci. Med. Sci. 55, 194B-200
   Abstract »    Full Text »
Induction of topoisomerase I cleavage complexes by 1-beta -D-arabinofuranosylcytosine (ara-C) in vitro and in ara-C-treated cells.
P. Pourquier, Y. Takebayashi, Y. Urasaki, C. Gioffre, G. Kohlhagen, and Y. Pommier (2000)
PNAS 97, 1885-1890
   Abstract »    Full Text »    PDF »
Comparison of In Vitro Activities of Camptothecin and Nitidine Derivatives against Fungal and Cancer Cells.
M. Del Poeta, S.-F. Chen, D. Von Hoff, C. C. Dykstra, M. C. Wani, G. Manikumar, J. Heitman, M. E. Wall, and J. R. Perfect (1999)
Antimicrob. Agents Chemother. 43, 2862-2868
   Abstract »    Full Text »
Domain Interactions Affecting Human DNA Topoisomerase I Catalysis and Camptothecin Sensitivity.
P. Fiorani, J. F. Amatruda, A. Silvestri, R. H. Butler, M.-A. Bjornsti, and P. Benedetti (1999)
Mol. Pharmacol. 56, 1105-1115
   Abstract »    Full Text »
A Functional Linker in Human Topoisomerase I Is Required for Maximum Sensitivity to Camptothecin in a DNA Relaxation Assay.
L. Stewart, G. C. Ireton, and J. J. Champoux (1999)
J. Biol. Chem. 274, 32950-32960
   Abstract »    Full Text »    PDF »
Antifungal Activities of Antineoplastic Agents: Saccharomyces cerevisiae as a Model System To Study Drug Action.
M. E. Cardenas, M. C. Cruz, M. Del Poeta, N. Chung, J. R. Perfect, and J. Heitman (1999)
Clin. Microbiol. Rev. 12, 583-611
   Abstract »    Full Text »    PDF »
CDC45 and DPB11 are required for processive DNA replication and resistance to DNA topoisomerase I-mediated DNA damage.
R. J. D. Reid, P. Fiorani, M. Sugawara, and M.-A. Bjornsti (1999)
PNAS 96, 11440-11445
   Abstract »    Full Text »    PDF »
Tethering a Type IB Topoisomerase to a DNA Site by Enzyme Fusion to a Heterologous Site-selective DNA-binding Protein Domain.
G. L. Beretta, M. Binaschi, E. Zagni, L. Capuani, and G. Capranico (1999)
Cancer Res. 59, 3689-3697
   Abstract »    Full Text »    PDF »
Asymmetric DNA bending in the Cre-loxP site-specific recombination synapse.
F. Guo, D. N. Gopaul, and G. D. Van Duyne (1999)
PNAS 96, 7143-7148
   Abstract »    Full Text »    PDF »
Topoisomerase I Is Essential in Cryptococcus neoformans: Role in Pathobiology and as an Antifungal Target.
M. Del Poeta, D. L. Toffaletti, T. H. Rude, C. C. Dykstra, J. Heitman, and J. R. Perfect (1999)
Genetics 152, 167-178
   Abstract »    Full Text »
Degradation of Topoisomerase I Induced by Topoisomerase I Inhibitors Is Dependent on Inhibitor Structure but Independent of Cell Death.
Q. Fu, S.-W. Kim, H.-X. Chen, S. Grill, and Y.-C. Cheng (1999)
Mol. Pharmacol. 55, 677-683
   Abstract »    Full Text »
Induction of Reversible Complexes between Eukaryotic DNA Topoisomerase I and DNA-containing Oxidative Base Damages. 7,8-DIHYDRO-8-OXOGUANINE AND 5-HYDROXYCYTOSINE.
P. Pourquier, L.-M. Ueng, J. Fertala, D. Wang, H.-J. Park, J. M. Essigmann, M.-A. Bjornsti, and Y. Pommier (1999)
J. Biol. Chem. 274, 8516-8523
   Abstract »    Full Text »    PDF »
Caspase-mediated Cleavage of DNA Topoisomerase I at Unconventional Sites during Apoptosis.
K. Samejima, P. A. Svingen, G. S. Basi, T. Kottke, P. W. Mesner Jr., L. Stewart, F. Durrieu, G. G. Poirier, E. S. Alnemri, J. J. Champoux, et al. (1999)
J. Biol. Chem. 274, 4335-4340
   Abstract »    Full Text »    PDF »
Intragenic Suppressors of Mutant DNA Topoisomerase I-induced Lethality Diminish Enzyme Binding of DNA.
C. L. Hann, A. L. Carlberg, and M.-A. Bjornsti (1998)
J. Biol. Chem. 273, 31519-31527
   Abstract »    Full Text »    PDF »
Flp Ribonuclease Activities. MECHANISTIC SIMILARITIES AND CONTRASTS TO SITE-SPECIFIC DNA RECOMBINATION.
C.-J. Xu, Y.-T. Ahn, S. Pathania, and M. Jayaram (1998)
J. Biol. Chem. 273, 30591-30598
   Abstract »    Full Text »    PDF »
The Activity of Topoisomerase I Is Modulated by Large T Antigen during Unwinding of the SV40 Origin.
D. T. Simmons, R. Roy, L. Chen, D. Gai, and P. W. Trowbridge (1998)
J. Biol. Chem. 273, 20390-20396
   Abstract »    Full Text »    PDF »
Crystal Structures of Human Topoisomerase I in Covalent and Noncovalent Complexes with DNA.
M. R. Redinbo, L. Stewart, P. Kuhn, J. J. Champoux, and W. G. Hol (1998)
Science 279, 1504-1513
   Abstract »    Full Text »
A Model for the Mechanism of Human Topoisomerase I.
L. Stewart, M. R. Redinbo, X. Qiu, W. G. Hol, and J. J. Champoux (1998)
Science 279, 1534-1541
   Abstract »    Full Text »
Inhibition of Flp Recombinase by the Topoisomerase I-targeting Drugs, Camptothecin and NSC-314622.
R. F. Frohlich, S. Gude Hansen, M. Lisby, I. Grainge, O. Westergaard, M. Jayaram, and B. R. Knudsen (2001)
J. Biol. Chem. 276, 6993-6997
   Abstract »    Full Text »    PDF »
Expression of Human Topoisomerase I with a Partial Deletion of the Linker Region Yields Monomeric and Dimeric Enzymes That Respond Differently to Camptothecin.
G. C. Ireton, L. Stewart, L. H. Parker, and J. J. Champoux (2000)
J. Biol. Chem. 275, 25820-25830
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)