Research Topics
Species | John NitissSummaryAffiliation: St. Jude Children's Research Hospital Country: USA Publications
Research Grants
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Publications
Human small cell lung cancer NYH cells resistant to the bisdioxopiperazine ICRF-187 exhibit a functional dominant Tyr165Ser mutation in the Walker A ATP binding site of topoisomerase II alphaIrene Wessel
Department of Pathology, Laboratory Center, Rigshospitalet 5431, DK-2100 Copenhagen, Denmark
FEBS Lett 520:161-6. 2002..These results enable a model of the bisdioxopiperazine pharmacophore using the proposed asymmetric ATP hydrolysis of the enzyme...- Investigating the biological functions of DNA topoisomerases in eukaryotic cellsJ L Nitiss
St Jude Children s Research Hospital, Molecular Pharmacology Department, 332 N Lauderdale, Memphis, TN 38105, USA
Biochim Biophys Acta 1400:63-81. 1998..These studies highlight the importance of understanding how topoisomerases participate in the normal processes of transcription, DNA replication, and genome stability... 
Targeting DNA topoisomerase II in cancer chemotherapyJohn L Nitiss
Molecular Pharmacology Department, St Jude Children s Research Hospital, Memphis, TN 38105, USA
Nat Rev Cancer 9:338-50. 2009..These studies promise refined targeting of TOP2 as an effective anticancer strategy...- DNA topoisomerase II and its growing repertoire of biological functionsJohn L Nitiss
Molecular Pharmacology Department, St Jude Children s Research Hospital, Memphis, TN 38105, USA
Nat Rev Cancer 9:327-37. 2009.... - Gimatecan (sigma-tau industrie farmaceutiche riunite/novartis)John L Nitiss
St Jude Children s Research Hospital, Molecular Pharmacology Department, 332 N Lauderdale Street, Memphis, TN 38105, USA
IDrugs 8:578-88. 2005..Sigma-Tau Industrie Farmaceutiche Riunite SpA and Novartis AG are developing oral gimatecan, a camptothecin derivative, for the potential treatment of tumors, including glioblastoma... - A mutation in human topoisomerase II alpha whose expression is lethal in DNA repair-deficient yeast cellsJerrylaine V Walker
Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
J Biol Chem 279:25947-54. 2004..This mutant enzyme also serves as a new model for understanding the action of drugs targeting topoisomerase II... - DNA topoisomerases in cancer chemotherapy: using enzymes to generate selective DNA damageJohn L Nitiss
Molecular Pharmacology Department, St Jude Children s Research Hospital, Memphis, TN 38105, USA
Curr Opin Investig Drugs 3:1512-6. 2002..These investigations into the mechanisms of action of topoisomerase-targeting agents should aid in the design of dinical protocols that optimize the activity of these agents... - A copper connection to the uptake of platinum anticancer drugsJohn L Nitiss
Molecular Pharmacology Department, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
Proc Natl Acad Sci U S A 99:13963-5. 2002 - Overexpression of type I topoisomerases sensitizes yeast cells to DNA damageJ L Nitiss
Molecular Pharmacology Department, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
J Biol Chem 276:26708-14. 2001..We suggest that TOP1 does not participate in the repair of DNA damage in yeast cells. However, the enzyme has the potential of exacerbating DNA damage by forming covalent DNA-protein complexes at sites of DNA damage... - Roles of nonhomologous end-joining pathways in surviving topoisomerase II-mediated DNA damageMobeen Malik
Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
Mol Cancer Ther 5:1405-14. 2006..Taken together, these results show a clear role for NHEJ in the repair of DNA damage induced by topoisomerase II-targeting agents and suggest that this pathway may participate in translocations generated by drugs, such as etoposide... - DNA repair functions that control sensitivity to topoisomerase-targeting drugsMobeen Malik
Department of Molecular Pharmacology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
Eukaryot Cell 3:82-90. 2004..cerevisiae system), our results highlight the usefulness of S. pombe in understanding how cells deal with the unique DNA damage induced by topoisomerases... - Isolation and characterization of mAMSA-hypersensitive mutants. Cytotoxicity of Top2 covalent complexes containing DNA single strand breaksAnna T Rogojina
Molecular Pharmacology Department, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
J Biol Chem 283:29239-50. 2008..These results indicate that generation of single strand breaks by Top2-targeting agents can be an important component of cell killing by Top2-targeting drugs... - Stability of the topoisomerase II closed clamp conformation may influence DNA-stimulated ATP hydrolysisJerrylaine Vaughn
Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
J Biol Chem 280:11920-9. 2005..We suggest that the DNA-stimulated ATPase of topoisomerase II is intimately connected with steps that occur while the N-terminal domain of the enzyme is dimerized... - Tyrosyl-DNA phosphodiesterase (Tdp1) participates in the repair of Top2-mediated DNA damageKarin C Nitiss
Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
Proc Natl Acad Sci U S A 103:8953-8. 2006..Our results show that Tdp1 plays more general roles in DNA repair than repair of Top1 mediated DNA damage, and may participate in repairing many types of base damage to DNA... - Enhancing drug accumulation in Saccharomyces cerevisiae by repression of pleiotropic drug resistance genes with chimeric transcription repressorsAlexander Stepanov
St Jude Children s Research Hospital, Molecular Pharmacology Department, 332 N Lauderdale, Memphis, TN 38105, USA
Mol Pharmacol 74:423-31. 2008.... - Activation of the unfolded protein response is necessary and sufficient for reducing topoisomerase IIalpha protein levels and decreasing sensitivity to topoisomerase-targeted drugsMiranda D Gray
Department of Molecular Pharmacology, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, Tennessee 38105, USA
Mol Pharmacol 68:1699-707. 2005.... - DNA topoisomerase II as a target for cancer chemotherapyJerrylaine V Walker
Department of Molecular Pharmacology, St. Jude Children's Research Hospital, 332 N. Lauderdale Street, Memphis, TN 38105, USA
Cancer Invest 20:570-89. 2002 - Mutation of a conserved active site residue converts tyrosyl-DNA phosphodiesterase I into a DNA topoisomerase I-dependent poisonXiaoping He
Department of Structural Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
J Mol Biol 372:1070-81. 2007..However, the distinct pattern of mutant Tdp1 activity evident in yeast cells, suggests a more severe defect in Tdp1H(432)N-catalyzed resolution of 3' phospho-adducts... - Yeast Tdp1 regulates the fidelity of nonhomologous end joiningKarim Bahmed
Molecular Pharmacology Department, St Jude Children s Research Hospital, Memphis, TN 38105, USA
Proc Natl Acad Sci U S A 107:4057-62. 2010.... - Repair of topoisomerase I-mediated DNA damageYves Pommier
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, Maryland 20892, USA
Prog Nucleic Acid Res Mol Biol 81:179-229. 2006 - Importance of the fourth alpha-helix within the CAP homology domain of type II topoisomerase for DNA cleavage site recognition and quinolone actionDirk Strumberg
Department of Internal Medicine and Medical Oncology, West German Cancer Center, University Medical School of Essen, 45122 Essen, Germany
Antimicrob Agents Chemother 46:2735-46. 2002..It also demonstrates that selective amino acid residues in the alpha4-helix are important in determining the activity and possibly the binding of quinolones to the topoisomerase II-DNA complexes... - Probing the role of linker substituents in bisdioxopiperazine analogs for activity against wild-type and mutant human topoisomerase II alphaAxelle Renodon-Corniere
Department of Pathology, Laboratory and Finsen Centres, Rigshospitalet, Copenhagen, Denmark
Mol Pharmacol 63:1159-68. 2003..We discuss the implications of these observations for the understanding of the mechanism of bisdioxopiperazine action on topoisomerase II... - Yeast recombination pathways triggered by topoisomerase II-mediated DNA breaksMichelle Sabourin
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA
Nucleic Acids Res 31:4373-84. 2003..Non-homologous end joining also was triggered by etoposide treatment, but this pathway was considerably less active than single-strand invasion and did not contribute significantly to cell survival in S.cerevisiae... - A dual mechanism of action of the anticancer agent F 11782 on human topoisomerase II alphaLars H Jensen
Department of Pathology, Laboratory Center, Rigshospitalet 5444, Frederik V s vej 11, DK 2100 Copenhagen, Denmark
Biochem Pharmacol 66:623-31. 2003..Our results suggest that topoisomerase II alpha is a target of F 11782 in vivo, and that F 11782 may act as a novel topoisomerase II poison... - A mutation in Escherichia coli DNA gyrase conferring quinolone resistance results in sensitivity to drugs targeting eukaryotic topoisomerase IIThomas Gruger
Department of Pharmaceutical Biology and Microbiology, Institute of Pharmacy, University of Hamburg, Germany
Antimicrob Agents Chemother 48:4495-504. 2004.... - Biochemical and proteomics approaches to characterize topoisomerase IIalpha cysteines and DNA as targets responsible for cisplatin-induced inhibition of topoisomerase IIalphaBrian B Hasinoff
Faculty of Pharmacy, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
Mol Pharmacol 67:937-47. 2005.... - Interaction of human DNA topoisomerase II alpha with DNA: quantification by surface plasmon resonanceAxelle Renodon-Corniere
Department of Pathology, Laboratory and Finsen Centers, Rigshospitalet 5444, DK 2100 Copenhagen, Denmark
Biochemistry 41:13395-402. 2002..In conclusion, SPR is able to (1) determine the kinetics of topoisomerase II with its DNA substrate and (2) quantify the enzyme's closed clamp formation under varying circumstances... - Analysis of bisdioxopiperazine dexrazoxane binding to human DNA topoisomerase II alpha: decreased binding as a mechanism of drug resistanceAxelle Renodon-Corniere
Department of Pathology, Laboratory and Finsen Centers, Rigshospitalet 5444, DK 2100 Copenhagen, Denmark
Biochemistry 42:9749-54. 2003..The direct correlation between the level of drug binding and dexrazoxane resistance is consistent with a decreased drug binding mechanism of action for these dexrazoxane resistance conferring mutations... - Antifungal activity of eupolauridine and its action on DNA topoisomerasesShabana I Khan
National Center for Natural Products Research, Department of Pharmacognosy, The University of Mississippi, University, Mississippi 38677, USA
Antimicrob Agents Chemother 46:1785-92. 2002..These results indicate that a major target for fungal cell killing by eupolauridine is DNA topoisomerase II rather than topoisomerase I, but does not exclude the possibility that the drug also acts against other targets...
Research Grants
- DNA REPAIR AND ANTITOPOISOMERASE DRUG EFFECTSJohn Nitiss; Fiscal Year: 2003..The experiments will also be important for understanding how topoisomerase targeting drugs lead to secondary malignancies. ..
- ANTI TOPOISOMERASE DRUG ACTION IN YEASTJohn Nitiss; Fiscal Year: 2004..This work is designed to provide insight into the biochemical mechanisms of anti- topoisomerase drug action, and may be useful in the development of new and more effective topoisomerase inhibitors. ..
- DNA REPAIR AND ANTITOPOISOMERASE DRUG EFFECTSJohn Nitiss; Fiscal Year: 2007..Answering these questions may also suggest strategies for circumventing resistance to these clinically important anticancer drugs. ..
- ANTI-TOPOISOMERASE DRUG ACTION IN YEASTJohn L Nitiss; Fiscal Year: 2010..The proposed studies will provide a detailed picture of how Top2 targeting drugs interact with the enzyme, and may lead to tools needed for designing safer and more effective drugs that target this enzyme. ..
- ANTITOPOISOMERASE DRUG ACTION IN YEASTJohn Nitiss; Fiscal Year: 1999..This work is designed to provide insight into the biochemical mechanisms of anti-topoisomerase drug action, and may be useful in the development of new and more effective topoisomerase inhibitors. ..
- DNA REPAIR AND ANTITOPOISOMERASE DRUG EFFECTSJohn L Nitiss; Fiscal Year: 2010..Answering these questions may also suggest strategies for circumventing resistance to these clinically important anticancer drugs. ..