MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
 QUICK SEARCH:   [advanced]


     


This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Eng, W. K.
Right arrow Articles by Sternglanz, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Eng, W. K.
Right arrow Articles by Sternglanz, R.

Evidence that DNA topoisomerase I is necessary for the cytotoxic effects of camptothecin

WK Eng, L Faucette, RK Johnson and R Sternglanz

Department of Biochemistry, State University of New York, Stony Brook 11794.

The budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe are both sensitive to camptothecin, an inhibitor of DNA topoisomerase I. An S. cerevisiae DNA repair mutant, rad52, is hypersensitive to the drug. In both species, topoisomerase I mutants totally lacking the enzyme are completely resistant to the drug. A strain with a mutation leading to a temperature-sensitive topoisomerase I exhibits temperature dependence in its in vivo response to camptothecin. A strain carrying a plasmid that overproduces topoisomerase I is hypersensitive to the drug. The rad52 mutant is killed by overproduction of the enzyme, even in the absence of the drug. The response of several of these strains to camptothecin analogs, to DNA topoisomerase II inhibitors, and to other drugs is reported. The cytotoxic effects of camptothecin are discussed in terms of the drug extending the lifetime of a topoisomerase I-DNA covalent intermediate, which is recognized as DNA damage by a DNA repair system.

Volume 34, Issue 6, pp. 755-760, 12/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
Mol. Pharmacol.Home page
L.-C. Ma, C.-C. Kuo, J.-F. Liu, L.-T. Chen, and J.-Y. Chang
Transcriptional Repression of O6-Methylguanine DNA Methyltransferase Gene Rendering Cells Hypersensitive to N,N'-Bis(2-chloroethyl)-N-nitrosurea in Camptothecin-Resistant Cells
Mol. Pharmacol., August 1, 2008; 74(2): 517 - 526.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
S. Sirikantaramas, M. Yamazaki, and K. Saito
From the Cover: Mutations in topoisomerase I as a self-resistance mechanism coevolved with the production of the anticancer alkaloid camptothecin in plants
PNAS, May 6, 2008; 105(18): 6782 - 6786.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
K. Takagi, T. S. Dexheimer, C. Redon, O. Sordet, K. Agama, G. Lavielle, A. Pierre, S. E. Bates, and Y. Pommier
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., December 1, 2007; 6(12): 3229 - 3238.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
C.-C. Kuo, J.-F. Liu, and J.-Y. Chang
DNA Repair Enzyme, O6-Methylguanine DNA Methyltransferase, Modulates Cytotoxicity of Camptothecin-Derived Topoisomerase I Inhibitors
J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 946 - 954.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
C. Marchand, S. Antony, K. W. Kohn, M. Cushman, A. Ioanoviciu, B. L. Staker, A. B. Burgin, L. Stewart, and Y. Pommier
A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex.
Mol. Cancer Ther., February 1, 2006; 5(2): 287 - 295.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
H. R. Jacquiau, R. C. A. M. van Waardenburg, R. J. D. Reid, M. H. Woo, H. Guo, E. S. Johnson, and M.-A. Bjornsti
Defects in SUMO (Small Ubiquitin-related Modifier) Conjugation and Deconjugation Alter Cell Sensitivity to DNA Topoisomerase I-induced DNA Damage
J. Biol. Chem., June 24, 2005; 280(25): 23566 - 23575.
[Abstract] [Full Text] [PDF]


Home page
Antimicrob. Agents Chemother.Home page
J.-F. Marquis, I. Hardy, and M. Olivier
Topoisomerase I Amino Acid Substitutions, Gly185Arg and Asp325Glu, Confer Camptothecin Resistance in Leishmania donovani
Antimicrob. Agents Chemother., April 1, 2005; 49(4): 1441 - 1446.
[Abstract] [Full Text] [PDF]


Home page
J Clin PharmacolHome page
A. Chatterjee, R. Digumarti, K. Katneni, V. V. Upreti, R. N. V. S. Mamidi, R. Mullangi, A. Surath, M. L. Srinivas, S. Uppalapati, S. Jiwatani, et al.
Safety, Tolerability, and Pharmacokinetics of a Capsule Formulation of DRF-1042, a Novel Camptothecin Analog, in Refractory Cancer Patients in a Bridging Phase I Study
J. Clin. Pharmacol., April 1, 2005; 45(4): 453 - 460.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
D. Yu, E. Khan, M. A. Khaleque, J. Lee, G. Laco, G. Kohlhagen, S. Kharbanda, Y.-C. Cheng, Y. Pommier, and A. Bharti
Phosphorylation of DNA Topoisomerase I by the c-Abl Tyrosine Kinase Confers Camptothecin Sensitivity
J. Biol. Chem., December 10, 2004; 279(50): 51851 - 51861.
[Abstract] [Full Text] [PDF]


Home page
Ann OncolHome page
K. Mross, H. Richly, N. Schleucher, S. Korfee, M. Tewes, M. E. Scheulen, S. Seeber, T. Beinert, M. Schweigert, U. Sauer, et al.
A phase I clinical and pharmacokinetic study of the camptothecin glycoconjugate, BAY 38-3441, as a daily infusion in patients with advanced solid tumors
Ann. Onc., August 1, 2004; 15(8): 1284 - 1294.
[Abstract] [Full Text] [PDF]


Home page
J Clin PharmacolHome page
A. Chatterjee, R. Digumarti, R. N. V. S. Mamidi, K. Katneni, V. V. Upreti, A. Surath, M. L. Srinivas, S. Uppalapati, S. Jiwatani, S. Subramaniam, et al.
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of an Orally Active Novel Camptothecin Analog, DRF-1042, in Refractory Cancer Patients in a Phase I Dose Escalation Study
J. Clin. Pharmacol., July 1, 2004; 44(7): 723 - 736.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
R. C.A.M. van Waardenburg, L. A. de Jong, F. van Delft, M. A.J. van Eijndhoven, M. Bohlander, M.-A. Bjornsti, J. Brouwer, and J. H.M. Schellens
Homologous recombination is a highly conserved determinant of the synergistic cytotoxicity between cisplatin and DNA topoisomerase I poisons
Mol. Cancer Ther., April 1, 2004; 3(4): 393 - 402.
[Abstract] [Full Text] [PDF]


Home page
Eukaryot CellHome page
M. Malik and J. L. Nitiss
DNA Repair Functions That Control Sensitivity to Topoisomerase-Targeting Drugs
Eukaryot. Cell, February 1, 2004; 3(1): 82 - 90.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
H. Interthal, P. M. Quigley, W. G. J. Hol, and J. J. Champoux
The Role of Lysine 532 in the Catalytic Mechanism of Human Topoisomerase I
J. Biol. Chem., January 23, 2004; 279(4): 2984 - 2992.
[Abstract] [Full Text] [PDF]


Home page
Ann OncolHome page
J. P. Braybrooke, E. Boven, N. P. Bates, R. Ruijter, N. Dobbs, P. D. Cheverton, H. M. Pinedo, and D. C. Talbot
Phase I and pharmacokinetic study of the topoisomerase I inhibitor, exatecan mesylate (DX-8951f ), using a weekly 30-minute intravenous infusion, in patients with advanced solid malignancies
Ann. Onc., June 1, 2003; 14(6): 913 - 921.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
S. A. Bastin-Shanower, W. M. Fricke, J. R. Mullen, and S. J. Brill
The Mechanism of Mus81-Mms4 Cleavage Site Selection Distinguishes It from the Homologous Endonuclease Rad1-Rad10
Mol. Cell. Biol., May 15, 2003; 23(10): 3487 - 3496.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
J.-Y. Chang, J.-F. Liu, S.-H. Juang, T.-W. Liu, and L.-T. Chen
Novel Mutation of Topoisomerase I in Rendering Cells Resistant to Camptothecin
Cancer Res., July 1, 2002; 62(13): 3716 - 3721.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
M. H. Woo, J. R. Vance, A. R. O. Marcos, C. Bailly, and M.-A. Bjornsti
Active Site Mutations in DNA Topoisomerase I Distinguish the Cytotoxic Activities of Camptothecin and the Indolocarbazole, Rebeccamycin
J. Biol. Chem., February 1, 2002; 277(6): 3813 - 3822.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
D. B. Longley, P. R. Ferguson, J. Boyer, T. Latif, M. Lynch, P. Maxwell, D. P. Harkin, and P. G. Johnston
Characterization of a Thymidylate Synthase (TS)-inducible Cell Line: A Model System for Studying Sensitivity to TS- and non-TS-targeted Chemotherapies
Clin. Cancer Res., November 1, 2001; 7(11): 3533 - 3539.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
B. A. Stohr and K. N. Kreuzer
Repair of Topoisomerase-Mediated DNA Damage in Bacteriophage T4
Genetics, May 1, 2001; 158(1): 19 - 28.
[Abstract] [Full Text]


Home page
Cancer Res.Home page
A. K. Larsen, C. Gilbert, G. Chyzak, S. Y. Plisov, I. Naguibneva, O. Lavergne, L. Lesueur-Ginot, and D. C. H. Bigg
Unusual Potency of BN 80915, a Novel Fluorinated E-ring Modified Camptothecin, toward Human Colon Carcinoma Cells
Cancer Res., April 1, 2001; 61(7): 2961 - 2967.
[Abstract] [Full Text]


Home page
JCOHome page
M. E. Royce, P. M. Hoff, P. Dumas, Y. Lassere, J. J. Lee, J. Coyle, M. P. Ducharme, R. De Jager, and R. Pazdur
Phase I and Pharmacokinetic Study of Exatecan Mesylate (DX-8951f): A Novel Camptothecin Analog
J. Clin. Oncol., March 1, 2001; 19(5): 1493 - 1500.
[Abstract] [Full Text] [PDF]


Home page
Ann. N. Y. Acad. Sci.Home page
A. SALEEM, T. K. EDWARDS, Z. RASHEED, and E. H. RUBIN
Mechanisms of Resistance to Camptothecins
Ann. N.Y. Acad. Sci., December 1, 2000; 922(1): 46 - 55.
[Abstract] [Full Text] [PDF]


Home page
Ann. N. Y. Acad. Sci.Home page
J. J. CHAMPOUX
Structure-Based Analysis of the Effects of Camptothecin on the Activities of Human Topoisomerase I
Ann. N.Y. Acad. Sci., December 1, 2000; 922(1): 56 - 64.
[Abstract] [Full Text] [PDF]


Home page
Ann. N. Y. Acad. Sci.Home page
P. FIORANI and M.-A. BJORNSTI
Mechanisms of DNA Topoisomerase I-Induced Cell Killing in the Yeast: Saccharomyces cerevisiae
Ann. N.Y. Acad. Sci., December 1, 2000; 922(1): 65 - 75.
[Abstract] [Full Text] [PDF]


Home page
Pharmacol. Rev.Home page
P. Perego, G. S. Jimenez, L. Gatti, S. B. Howell, and F. Zunino
Yeast Mutants As a Model System for Identification of Determinants of Chemosensitivity
Pharmacol. Rev., December 1, 2000; 52(4): 477 - 492.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
D. Strumberg, A. A. Pilon, M. Smith, R. Hickey, L. Malkas, and Y. Pommier
Conversion of Topoisomerase I Cleavage Complexes on the Leading Strand of Ribosomal DNA into 5'-Phosphorylated DNA Double-Strand Breaks by Replication Runoff
Mol. Cell. Biol., June 1, 2000; 20(11): 3977 - 3987.
[Abstract] [Full Text]


Home page
J. Biol. Chem.Home page
J. Fertala, J. R. Vance, P. Pourquier, Y. Pommier, and M.-A. Bjornsti
Substitutions of Asn-726 in the Active Site of Yeast DNA Topoisomerase I Define Novel Mechanisms of Stabilizing the Covalent Enzyme-DNA Intermediate
J. Biol. Chem., May 12, 2000; 275(20): 15246 - 15253.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
M. J. A. de Jonge, W. J. Loos, H. Gelderblom, A. S. Th. Planting, M. E. L. van der Burg, A. Sparreboom, E. Brouwer, V. van Beurden, M. A. Mantel, E. Doyle, et al.
Phase I Pharmacologic Study of Oral Topotecan and Intravenous Cisplatin: Sequence-Dependent Hematologic Side Effects
J. Clin. Oncol., May 10, 2000; 18(10): 2104 - 2115.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
L. H. Jensen, K. C. Nitiss, A. Rose, J. Dong, J. Zhou, T. Hu, N. Osheroff, P. B. Jensen, M. Sehested, and J. L. Nitiss
A Novel Mechanism of Cell Killing by Anti-topoisomerase II Bisdioxopiperazines
J. Biol. Chem., January 21, 2000; 275(3): 2137 - 2146.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
G. Hong and K. N. Kreuzer
An Antitumor Drug-Induced Topoisomerase Cleavage Complex Blocks a Bacteriophage T4 Replication Fork In Vivo
Mol. Cell. Biol., January 15, 2000; 20(2): 594 - 603.
[Abstract] [Full Text]


Home page
JCOHome page
M. J. A. de Jonge, A. Sparreboom, A. S. T. Planting, M. E. L. van der Burg, M. M. de Boer-Dennert, J. t. Steeg, C. Jacques, and J. Verweij
Phase I Study of 3-Week Schedule of Irinotecan Combined With Cisplatin in Patients With Advanced Solid Tumors
J. Clin. Oncol., January 5, 2000; 18(1): 187 - 187.
[Abstract] [Full Text] [PDF]


Home page
Antimicrob. Agents Chemother.Home page
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
Comparison of In Vitro Activities of Camptothecin and Nitidine Derivatives against Fungal and Cancer Cells
Antimicrob. Agents Chemother., December 1, 1999; 43(12): 2862 - 2868.
[Abstract] [Full Text]


Home page
J. Biol. Chem.Home page
L. Stewart, G. C. Ireton, and J. J. Champoux
A Functional Linker in Human Topoisomerase I Is Required for Maximum Sensitivity to Camptothecin in a DNA Relaxation Assay
J. Biol. Chem., November 12, 1999; 274(46): 32950 - 32960.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
M. Ducreux, M. Ychou, J.-F. Seitz, M. Bonnay, A. Bexon, J.-P. Armand, M. Mahjoubi, D. Mery-Mignard, and P. Rougier
Irinotecan Combined With Bolus Fluorouracil, Continuous Infusion Fluorouracil, and High-Dose Leucovorin Every Two Weeks (LV5FU2 Regimen): A Clinical Dose-Finding and Pharmacokinetic Study in Patients With Pretreated Metastatic Colorectal Cancer
J. Clin. Oncol., September 1, 1999; 17(9): 2901 - 2901.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
C. Walowsky, D. J. Fitzhugh, I. B. Castano, J. Y. Ju, N. A. Levin, and M. F. Christman
The Topoisomerase-related Function Gene TRF4 Affects Cellular Sensitivity to the Antitumor Agent Camptothecin
J. Biol. Chem., March 12, 1999; 274(11): 7302 - 7308.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
R. L. Drengler, J. G. Kuhn, L. J. Schaaf, G. I. Rodriguez, M. A. Villalona-Calero, L. A. Hammond, J. A. Stephenson Jr., S. Hodges, M. A. Kraynak, B. A. Staton, et al.
Phase I and Pharmacokinetic Trial of Oral Irinotecan Administered Daily for 5 Days Every 3 Weeks in Patients With Solid Tumors
J. Clin. Oncol., February 1, 1999; 17(2): 685 - 685.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
O. Wildner, R. M. Blaese, and J. C. Morris
Therapy of Colon Cancer with Oncolytic Adenovirus Is Enhanced by the Addition of Herpes Simplex Virus-thymidine kinase
Cancer Res., January 1, 1999; 59(2): 410 - 413.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
C. Hann, D. L. Evans, J. Fertala, P. Benedetti, M.-A. Bjornsti, and D. J. Hall
Increased Camptothecin Toxicity Induced in Mammalian Cells Expressing Saccharomyces cerevisiae DNA Topoisomerase I
J. Biol. Chem., April 3, 1998; 273(14): 8425 - 8433.
[Abstract] [Full Text] [PDF]


Home page
The OncologistHome page
L. B. Saltz
Clinical Use of Irinotecan:Current Status and Future Considerations
Oncologist, December 1, 1997; 2(6): 402 - 409.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
M. D. Megonigal, J. Fertala, and M.-A. Bjornsti
Alterations in the Catalytic Activity of Yeast DNA Topoisomerase I Result in Cell Cycle Arrest and Cell Death
J. Biol. Chem., May 9, 1997; 272(19): 12801 - 12808.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
R. J. D. Reid, E. A. Kauh, and M.-A. Bjornsti
Camptothecin Sensitivity Is Mediated by the Pleiotropic Drug Resistance Network in Yeast
J. Biol. Chem., May 2, 1997; 272(18): 12091 - 12099.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
C. S. Hemenway and J. Heitman
Immunosuppressant Target Protein FKBP12 Is Required for P-Glycoprotein Function in Yeast
J. Biol. Chem., August 2, 1996; 271(31): 18527 - 18534.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
A. M. Knab, J. Fertala, and M.-A. Bjornsti
A Camptothecin-resistant DNA Topoisomerase I Mutant Exhibits Altered Sensitivities to Other DNA Topoisomerase Poisons
J. Biol. Chem., March 17, 1995; 270(11): 6141 - 6148.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
G. C. Ireton, L. Stewart, L. H. Parker, and J. J. Champoux
Expression of Human Topoisomerase I with a Partial Deletion of the Linker Region Yields Monomeric and Dimeric Enzymes That Respond Differently to Camptothecin
J. Biol. Chem., August 11, 2000; 275(33): 25820 - 25830.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
T. K. Edwards, A. Saleem, J. A. Shaman, T. Dennis, C. Gerigk, E. Oliveros, M. R. Gartenberg, and E. H. Rubin
Role for Nucleolin/Nsr1 in the Cellular Localization of Topoisomerase I
J. Biol. Chem., November 10, 2000; 275(46): 36181 - 36188.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
M. Lisby, J. R. Olesen, C. Skouboe, B. O. Krogh, T. Straub, F. Boege, S. Velmurugan, P. M. Martensen, A. H. Andersen, M. Jayaram, et al.
Residues within the N-terminal Domain of Human Topoisomerase I Play a Direct Role in Relaxation*
J. Biol. Chem., June 1, 2001; 276(23): 20220 - 20227.
[Abstract] [Full Text] [PDF]




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
 Molecular Interventions Drug Metabolism and Disposition

Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics