John Nitiss

Summary

Affiliation: St. Jude Children's Research Hospital
Country: USA

Publications

  1. ncbi request reprint 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 alpha
    Irene Wessel
    Department of Pathology, Laboratory Center, Rigshospitalet 5431, DK 2100 Copenhagen, Denmark
    FEBS Lett 520:161-6. 2002
  2. ncbi request reprint Investigating the biological functions of DNA topoisomerases in eukaryotic cells
    J 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
  3. pmc Targeting DNA topoisomerase II in cancer chemotherapy
    John L Nitiss
    Molecular Pharmacology Department, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Nat Rev Cancer 9:338-50. 2009
  4. pmc DNA topoisomerase II and its growing repertoire of biological functions
    John L Nitiss
    Molecular Pharmacology Department, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Nat Rev Cancer 9:327-37. 2009
  5. ncbi request reprint 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
  6. ncbi request reprint A mutation in human topoisomerase II alpha whose expression is lethal in DNA repair-deficient yeast cells
    Jerrylaine V Walker
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Biol Chem 279:25947-54. 2004
  7. ncbi request reprint DNA topoisomerases in cancer chemotherapy: using enzymes to generate selective DNA damage
    John L Nitiss
    Molecular Pharmacology Department, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Curr Opin Investig Drugs 3:1512-6. 2002
  8. pmc A copper connection to the uptake of platinum anticancer drugs
    John 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
  9. ncbi request reprint Overexpression of type I topoisomerases sensitizes yeast cells to DNA damage
    J L Nitiss
    Molecular Pharmacology Department, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Biol Chem 276:26708-14. 2001
  10. ncbi request reprint Roles of nonhomologous end-joining pathways in surviving topoisomerase II-mediated DNA damage
    Mobeen 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

Research Grants

  1. DNA REPAIR AND ANTITOPOISOMERASE DRUG EFFECTS
    John Nitiss; Fiscal Year: 2003
  2. ANTI TOPOISOMERASE DRUG ACTION IN YEAST
    John Nitiss; Fiscal Year: 2004
  3. DNA REPAIR AND ANTITOPOISOMERASE DRUG EFFECTS
    John Nitiss; Fiscal Year: 2007
  4. ANTI-TOPOISOMERASE DRUG ACTION IN YEAST
    John L Nitiss; Fiscal Year: 2010
  5. ANTITOPOISOMERASE DRUG ACTION IN YEAST
    John Nitiss; Fiscal Year: 1999
  6. DNA REPAIR AND ANTITOPOISOMERASE DRUG EFFECTS
    John L Nitiss; Fiscal Year: 2010

Collaborators

Detail Information

Publications29

  1. ncbi request reprint 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 alpha
    Irene 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...
  2. ncbi request reprint Investigating the biological functions of DNA topoisomerases in eukaryotic cells
    J 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...
  3. pmc Targeting DNA topoisomerase II in cancer chemotherapy
    John 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...
  4. pmc DNA topoisomerase II and its growing repertoire of biological functions
    John L Nitiss
    Molecular Pharmacology Department, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Nat Rev Cancer 9:327-37. 2009
    ....
  5. ncbi request reprint 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...
  6. ncbi request reprint A mutation in human topoisomerase II alpha whose expression is lethal in DNA repair-deficient yeast cells
    Jerrylaine 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...
  7. ncbi request reprint DNA topoisomerases in cancer chemotherapy: using enzymes to generate selective DNA damage
    John 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...
  8. pmc A copper connection to the uptake of platinum anticancer drugs
    John 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
  9. ncbi request reprint Overexpression of type I topoisomerases sensitizes yeast cells to DNA damage
    J 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...
  10. ncbi request reprint Roles of nonhomologous end-joining pathways in surviving topoisomerase II-mediated DNA damage
    Mobeen 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...
  11. pmc DNA repair functions that control sensitivity to topoisomerase-targeting drugs
    Mobeen 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...
  12. pmc Isolation and characterization of mAMSA-hypersensitive mutants. Cytotoxicity of Top2 covalent complexes containing DNA single strand breaks
    Anna 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...
  13. ncbi request reprint Stability of the topoisomerase II closed clamp conformation may influence DNA-stimulated ATP hydrolysis
    Jerrylaine 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...
  14. pmc Tyrosyl-DNA phosphodiesterase (Tdp1) participates in the repair of Top2-mediated DNA damage
    Karin 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...
  15. pmc Enhancing drug accumulation in Saccharomyces cerevisiae by repression of pleiotropic drug resistance genes with chimeric transcription repressors
    Alexander Stepanov
    St Jude Children s Research Hospital, Molecular Pharmacology Department, 332 N Lauderdale, Memphis, TN 38105, USA
    Mol Pharmacol 74:423-31. 2008
    ....
  16. ncbi request reprint Activation of the unfolded protein response is necessary and sufficient for reducing topoisomerase IIalpha protein levels and decreasing sensitivity to topoisomerase-targeted drugs
    Miranda 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
    ....
  17. ncbi request reprint DNA topoisomerase II as a target for cancer chemotherapy
    Jerrylaine 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
  18. ncbi request reprint Mutation of a conserved active site residue converts tyrosyl-DNA phosphodiesterase I into a DNA topoisomerase I-dependent poison
    Xiaoping 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...
  19. pmc Yeast Tdp1 regulates the fidelity of nonhomologous end joining
    Karim 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
    ....
  20. pmc Repair of topoisomerase I-mediated DNA damage
    Yves 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
  21. pmc Importance of the fourth alpha-helix within the CAP homology domain of type II topoisomerase for DNA cleavage site recognition and quinolone action
    Dirk 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...
  22. ncbi request reprint Probing the role of linker substituents in bisdioxopiperazine analogs for activity against wild-type and mutant human topoisomerase II alpha
    Axelle 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...
  23. pmc Yeast recombination pathways triggered by topoisomerase II-mediated DNA breaks
    Michelle 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...
  24. ncbi request reprint A dual mechanism of action of the anticancer agent F 11782 on human topoisomerase II alpha
    Lars 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...
  25. pmc A mutation in Escherichia coli DNA gyrase conferring quinolone resistance results in sensitivity to drugs targeting eukaryotic topoisomerase II
    Thomas Gruger
    Department of Pharmaceutical Biology and Microbiology, Institute of Pharmacy, University of Hamburg, Germany
    Antimicrob Agents Chemother 48:4495-504. 2004
    ....
  26. ncbi request reprint Biochemical and proteomics approaches to characterize topoisomerase IIalpha cysteines and DNA as targets responsible for cisplatin-induced inhibition of topoisomerase IIalpha
    Brian B Hasinoff
    Faculty of Pharmacy, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
    Mol Pharmacol 67:937-47. 2005
    ....
  27. ncbi request reprint Interaction of human DNA topoisomerase II alpha with DNA: quantification by surface plasmon resonance
    Axelle 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...
  28. ncbi request reprint Analysis of bisdioxopiperazine dexrazoxane binding to human DNA topoisomerase II alpha: decreased binding as a mechanism of drug resistance
    Axelle 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...
  29. pmc Antifungal activity of eupolauridine and its action on DNA topoisomerases
    Shabana 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 Grants21

  1. DNA REPAIR AND ANTITOPOISOMERASE DRUG EFFECTS
    John Nitiss; Fiscal Year: 2003
    ..The experiments will also be important for understanding how topoisomerase targeting drugs lead to secondary malignancies. ..
  2. ANTI TOPOISOMERASE DRUG ACTION IN YEAST
    John 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. ..
  3. DNA REPAIR AND ANTITOPOISOMERASE DRUG EFFECTS
    John Nitiss; Fiscal Year: 2007
    ..Answering these questions may also suggest strategies for circumventing resistance to these clinically important anticancer drugs. ..
  4. ANTI-TOPOISOMERASE DRUG ACTION IN YEAST
    John 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. ..
  5. ANTITOPOISOMERASE DRUG ACTION IN YEAST
    John 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. ..
  6. DNA REPAIR AND ANTITOPOISOMERASE DRUG EFFECTS
    John L Nitiss; Fiscal Year: 2010
    ..Answering these questions may also suggest strategies for circumventing resistance to these clinically important anticancer drugs. ..