Photo of Dr. John L Nitiss

John L Nitiss

Professor, Assistant Dean, Research at Rockford, Biopharmaceutical Sciences


Building & Room:



1601 Parkview Avenue, Rockford, IL, 61107

Office Phone:

(815) 395-5583

Office Phone TTY:

(815) 395-5743

Office Phone:

(815) 395-5788


DNA topoisomerases as targets for cancer chemotherapy.
Mechanisms of DNA repair by non-homologous end-joining.
Using yeast to study the action of therapeutic agents.
Roles of topoisomerases and other replication proteins in chromosme segregation and genome stability.

Selected Publications

  • Heo J, Li J, Summerlin MB, Hays A, Katyal S, McKinnon PJ, Nitiss KC, Nitiss JL, Hanakahi L. TDP1 promotes assembly of non-homologous end joining protein complexes on DNA.. DNA Repair. 2015;30:28-37. doi:10.1016/j.dnarep.2015.03.003.
  • Nitiss KC, Nitiss JL. Twisting and ironing: doxorubicin cardiotoxicity by mitochondrial DNA damage.. Clinical Cancer Research : an official journal of the American Association for Cancer Research. 2014;20(18):4737-9. doi:10.1158/1078-0432.CCR-14-0821.
  • Gao R, Schellenberg MJ, Huang SY, Abdelmalak M, Marchand C, Nitiss KC, Nitiss JL, Williams RS, Pommier Y. Proteolytic degradation of topoisomerase II (Top2) enables the processing of Top2·DNA and Top2·RNA covalent complexes by tyrosyl-DNA-phosphodiesterase 2 (TDP2).. The Journal of Biological Chemistry. 2014;289(26):17960-9. doi:10.1074/jbc.M114.565374.
  • Katyal S, Lee Y, Nitiss KC, Downing SM, Li Y, Shimada M, Zhao J, Russell HR, Petrini JH, Nitiss JL, McKinnon PJ. Aberrant topoisomerase-1 DNA lesions are pathogenic in neurodegenerative genome instability syndromes.. Nature Neuroscience. 2014;17(6):813-21. doi:10.1038/nn.3715.
  • Nitiss JL, Nitiss KC. Tdp2: a means to fixing the ends.. PLoS Genetics. 2013;9(3):e1003370. doi:10.1371/journal.pgen.1003370.
  • Hasinoff BB, Wu X, Nitiss JL, Kanagasabai R, Yalowich JC. The anticancer multi-kinase inhibitor dovitinib also targets topoisomerase I and topoisomerase II.. Biochemical Pharmacology. 2012;84(12):1617-26. doi:10.1016/j.bcp.2012.09.023.
  • Nitiss JL, Soans E, Rogojina A, Seth A, Mishina M. Topoisomerase assays.. Current protocols in pharmacology / editorial board, S.J. Enna (editor-in-chief) … [et al.]. 2012;Chapter 3:Unit 3.3.. doi:10.1002/0471141755.ph0303s57.
  • Chee GL, Bhattarai B, Daniel Gietz R, Alrushaid S, Nitiss JL, Hasinoff BB. Chemical reactivity and microbicidal action of bethoxazin.. Bioorganic & medicinal chemistry. 2012;20(4):1494-501. doi:10.1016/j.bmc.2011.12.051.
  • Bahmed K, Seth A, Nitiss KC, Nitiss JL. End-processing during non-homologous end-joining: a role for exonuclease 1.. Nucleic acids research. 2011;39(3):970-8. doi:10.1093/nar/gkq886.
  • Bahmed K, Nitiss KC, Nitiss JL. Yeast Tdp1 regulates the fidelity of nonhomologous end joining.. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(9):4057-62. doi:10.1073/pnas.0909917107.
  • Bahmed K, Nitiss KC, Nitiss JL. UnTTrapping the ends: a new player in overcoming protein linked DNA damage.. Cell research. 2010;20(2):122-3. doi:10.1038/cr.2010.17.
  • Nitiss JL. DNA topoisomerase II and its growing repertoire of biological functions.. Nature reviews. Cancer. 2009;9(5):327-37. doi:10.1038/nrc2608.
  • Nitiss JL. Targeting DNA topoisomerase II in cancer chemotherapy.. Nature reviews. Cancer. 2009;9(5):338-50. doi:10.1038/nrc2607.
  • Rogojina AT, Nitiss JL. Isolation and characterization of mAMSA-hypersensitive mutants. Cytotoxicity of Top2 covalent complexes containing DNA single strand breaks.. The Journal of biological chemistry. 2008;283(43):29239-50. doi:10.1074/jbc.M804058200.
  • Stepanov A, Nitiss KC, Neale G, Nitiss JL. Enhancing drug accumulation in Saccharomyces cerevisiae by repression of pleiotropic drug resistance genes with chimeric transcription repressors.. Molecular pharmacology. 2008;74(2):423-31. doi:10.1124/mol.107.044651.
  • Morgan-Linnell SK, Hiasa H, Zechiedrich L, Nitiss JL. Assessing sensitivity to antibacterial topoisomerase II inhibitors.. Current protocols in pharmacology / editorial board, S.J. Enna (editor-in-chief) … [et al.]. 2007;Chapter 3:Unit3.13. doi:10.1002/0471141755.ph0313s39.
  • He X, van Waardenburg RC, Babaoglu K, Price AC, Nitiss KC, Nitiss JL, Bjornsti MA, White SW. Mutation of a conserved active site residue converts tyrosyl-DNA phosphodiesterase I into a DNA topoisomerase I-dependent poison.. Journal of molecular biology. 2007;372(4):1070-81. doi:10.1016/j.jmb.2007.07.055.
  • Nitiss KC, Malik M, He X, White SW, Nitiss JL. Tyrosyl-DNA phosphodiesterase (Tdp1) participates in the repair of Top2-mediated DNA damage.. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(24):8953-8. doi:10.1073/pnas.0603455103.
  • Malik M, Nitiss KC, Enriquez-Rios V, Nitiss JL. Roles of nonhomologous end-joining pathways in surviving topoisomerase II-mediated DNA damage.. Molecular cancer therapeutics. 2006;5(6):1405-14. doi:10.1158/1535-7163.MCT-05-0263.
  • Pommier Y, Barcelo JM, Rao VA, Sordet O, Jobson AG, Thibaut L, Miao ZH, Seiler JA, Zhang H, Marchand C, Agama K, Nitiss JL, Redon C. Repair of topoisomerase I-mediated DNA damage.. Progress in nucleic acid research and molecular biology. 2006;81:179-229. doi:10.1016/S0079-6603(06)81005-6.
  • Gray MD, Mann M, Nitiss JL, Hendershot LM. Activation of the unfolded protein response is necessary and sufficient for reducing topoisomerase IIalpha protein levels and decreasing sensitivity to topoisomerase-targeted drugs.. Molecular pharmacology. 2005;68(6):1699-707. doi:10.1124/mol.105.014753.
  • Nitiss JL, Nitiss KC. Gimatecan (sigma-tau industrie farmaceutiche riunite/novartis).. IDrugs : the investigational drugs journal. 2005;8(7):578-88.
  • Vaughn J, Huang S, Wessel I, Sorensen TK, Hsieh T, Jensen LH, Jensen PB, Sehested M, Nitiss JL. Stability of the topoisomerase II closed clamp conformation may influence DNA-stimulated ATP hydrolysis.. The Journal of biological chemistry. 2005;280(12):11920-9. doi:10.1074/jbc.M411841200.
  • Hasinoff BB, Wu X, Krokhin OV, Ens W, Standing KG, Nitiss JL, Sivaram T, Giorgianni A, Yang S, Jiang Y, Yalowich JC. Biochemical and proteomics approaches to characterize topoisomerase IIalpha cysteines and DNA as targets responsible for cisplatin-induced inhibition of topoisomerase IIalpha.. Molecular pharmacology. 2005;67(3):937-47. doi:10.1124/mol.104.004416.
  • Gruger T, Nitiss JL, Maxwell A, Zechiedrich EL, Heisig P, Seeber S, Pommier Y, Strumberg D. A mutation in Escherichia coli DNA gyrase conferring quinolone resistance results in sensitivity to drugs targeting eukaryotic topoisomerase II.. Antimicrobial agents and chemotherapy. 2004;48(12):4495-504. doi:10.1128/AAC.48.12.4495-4504.2004.
  • Walker JV, Nitiss KC, Jensen LH, Mayne C, Hu T, Jensen PB, Sehested M, Hsieh T, Nitiss JL. A mutation in human topoisomerase II alpha whose expression is lethal in DNA repair-deficient yeast cells.. The Journal of biological chemistry. 2004;279(25):25947-54. doi:10.1074/jbc.M312314200.
  • Malik M, Nitiss JL. DNA repair functions that control sensitivity to topoisomerase-targeting drugs.. Eukaryotic cell. 2004;3(1):82-90.
  • Renodon-Cornière A, Jensen LH, Nitiss JL, Jensen PB, Sehested M. Analysis of bisdioxopiperazine dexrazoxane binding to human DNA topoisomerase II alpha: decreased binding as a mechanism of drug resistance.. Biochemistry. 2003;42(32):9749-54. doi:10.1021/bi034557d.
  • Jensen LH, Renodon-Cornière A, Nitiss KC, Hill BT, Nitiss JL, Jensen PB, Sehested M. A dual mechanism of action of the anticancer agent F 11782 on human topoisomerase II alpha.. Biochemical pharmacology. 2003;66(4):623-31.
  • Sabourin M, Nitiss JL, Nitiss KC, Tatebayashi K, Ikeda H, Osheroff N. Yeast recombination pathways triggered by topoisomerase II-mediated DNA breaks.. Nucleic acids research. 2003;31(15):4373-84.
  • Renodon-Cornière A, Sørensen TK, Jensen PB, Nitiss JL, Søkilde B, Sehested M, Jensen LH. Probing the role of linker substituents in bisdioxopiperazine analogs for activity against wild-type and mutant human topoisomerase II alpha.. Molecular pharmacology. 2003;63(5):1159-68.
  • Renodon-Cornière A, Jensen LH, Nitiss JL, Jensen PB, Sehested M. Interaction of human DNA topoisomerase II alpha with DNA: quantification by surface plasmon resonance.. Biochemistry. 2002;41(45):13395-402.
  • Nitiss JL. A copper connection to the uptake of platinum anticancer drugs.. Proceedings of the National Academy of Sciences of the United States of America. 2002;99(22):13963-5. doi:10.1073/pnas.232574299.
  • Nitiss JL. DNA topoisomerases in cancer chemotherapy: using enzymes to generate selective DNA damage.. Current opinion in investigational drugs (London, England : 2000). 2002;3(10):1512-6.
  • Strumberg D, Nitiss JL, Dong J, Walker J, Nicklaus MC, Kohn KW, Heddle JG, Maxwell A, Seeber S, Pommier Y. Importance of the fourth alpha-helix within the CAP homology domain of type II topoisomerase for DNA cleavage site recognition and quinolone action.. Antimicrobial agents and chemotherapy. 2002;46(9):2735-46.
  • Wessel I, Jensen LH, Renodon-Corniere A, Sorensen TK, Nitiss JL, Jensen PB, Sehested M. 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.. FEBS letters. 2002;520(1-3):161-6.
  • Khan SI, Nimrod AC, Mehrpooya M, Nitiss JL, Walker LA, Clark AM. Antifungal activity of eupolauridine and its action on DNA topoisomerases.. Antimicrobial agents and chemotherapy. 2002;46(6):1785-92.
  • Walker JV, Nitiss JL. DNA topoisomerase II as a target for cancer chemotherapy.. Cancer investigation. 2002;20(4):570-89.
  • Rothenborg-Jensen L, Hansen HF, Wessel I, Nitiss JL, Schmidt G, Jensen PB, Sehested M, Jensen LH. Linker length in podophyllotoxin-acridine conjugates determines potency in vivo and in vitro as well as specificity against MDR cell lines.. Anti-cancer drug design. 2001;16(6):305-15.
  • Nitiss JL, Nitiss KC, Rose A, Waltman JL. Overexpression of type I topoisomerases sensitizes yeast cells to DNA damage.. The Journal of biological chemistry. 2001;276(28):26708-14. doi:10.1074/jbc.M102674200.
  • Nitiss JL. Topoisomerase assays.. Current protocols in pharmacology / editorial board, S.J. Enna (editor-in-chief) … [et al.]. 2001;Chapter 3:Unit3.3. doi:10.1002/0471141755.ph0303s00.
  • Pourquier P, Waltman JL, Urasaki Y, Loktionova NA, Pegg AE, Nitiss JL, Pommier Y. Topoisomerase I-mediated cytotoxicity of N-methyl-N’-nitro-N-nitrosoguanidine: trapping of topoisomerase I by the O6-methylguanine.. Cancer research. 2001;61(1):53-8.
  • Nitiss JL, Nitiss KC. Yeast systems for demonstrating the targets of anti-topoisomerase II agents.. Methods in molecular biology (Clifton, N.J.). 2001;95:315-27.
  • Krynetskaia NF, Cai X, Nitiss JL, Krynetski EY, Relling MV. Thioguanine substitution alters DNA cleavage mediated by topoisomerase II.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2000;14(14):2339-44. doi:10.1096/fj.00-0089com.
  • Jensen LH, Wessel I, Møller M, Nitiss JL, Sehested M, Jensen PB. N-terminal and core-domain random mutations in human topoisomerase II alpha conferring bisdioxopiperazine resistance.. FEBS letters. 2000;480(2-3):201-7.
  • Dong J, Walker J, Nitiss JL. A mutation in yeast topoisomerase II that confers hypersensitivity to multiple classes of topoisomerase II poisons.. The Journal of biological chemistry. 2000;275(11):7980-7.
  • Jensen LH, Nitiss KC, Rose A, Dong J, Zhou J, Hu T, Osheroff N, Jensen PB, Sehested M, Nitiss JL. A novel mechanism of cell killing by anti-topoisomerase II bisdioxopiperazines.. The Journal of biological chemistry. 2000;275(3):2137-46.
  • Byl JA, Fortune JM, Burden DA, Nitiss JL, Utsugi T, Yamada Y, Osheroff N. DNA topoisomerases as targets for the anticancer drug TAS-103: primary cellular target and DNA cleavage enhancement.. Biochemistry. 1999;38(47):15573-9.
  • Strumberg D, Nitiss JL, Dong J, Kohn KW, Pommier Y. Molecular analysis of yeast and human type II topoisomerases. Enzyme-DNA and drug interactions.. The Journal of biological chemistry. 1999;274(40):28246-55.
  • Mao Y, Yu C, Hsieh TS, Nitiss JL, Liu AA, Wang H, Liu LF. Mutations of human topoisomerase II alpha affecting multidrug resistance and sensitivity.. Biochemistry. 1999;38(33):10793-800. doi:10.1021/bi9909804.
  • Wessel I, Jensen LH, Jensen PB, Falck J, Rose A, Roerth M, Nitiss JL, Sehested M. Human small cell lung cancer NYH cells selected for resistance to the bisdioxopiperazine topoisomerase II catalytic inhibitor ICRF-187 demonstrate a functional R162Q mutation in the Walker A consensus ATP binding domain of the alpha isoform.. Cancer research. 1999;59(14):3442-50.
  • Strumberg D, Nitiss JL, Rose A, Nicklaus MC, Pommier Y. Mutation of a conserved serine residue in a quinolone-resistant type II topoisomerase alters the enzyme-DNA and drug interactions.. The Journal of biological chemistry. 1999;274(11):7292-301.
  • Ramsewak RS, Nair MG, Strasburg GM, DeWitt DL, Nitiss JL. Biologically active carbazole alkaloids from Murraya koenigii.. Journal of agricultural and food chemistry. 1999;47(2):444-7.
  • Sabourin M, Byl JA, Hannah SE, Nitiss JL, Osheroff N. A mutant yeast topoisomerase II (top2G437S) with differential sensitivity to anticancer drugs in the presence and absence of ATP.. The Journal of biological chemistry. 1998;273(44):29086-92.
  • Nitiss JL. Investigating the biological functions of DNA topoisomerases in eukaryotic cells.. Biochimica et biophysica acta. 1998;1400(1-3):63-81.
  • Sehested M, Wessel I, Jensen LH, Holm B, Oliveri RS, Kenwrick S, Creighton AM, Nitiss JL, Jensen PB. Chinese hamster ovary cells resistant to the topoisomerase II catalytic inhibitor ICRF-159: a Tyr49Phe mutation confers high-level resistance to bisdioxopiperazines.. Cancer research. 1998;58(7):1460-8.
  • Nitiss JL, Zhou J, Rose A, Hsiung Y, Gale KC, Osheroff N. The bis(naphthalimide) DMP-840 causes cytotoxicity by its action against eukaryotic topoisomerase II.. Biochemistry. 1998;37(9):3078-85. doi:10.1021/bi9723257.
  • Nitiss JL, Pourquier P, Pommier Y. Aclacinomycin A stabilizes topoisomerase I covalent complexes.. Cancer research. 1997;57(20):4564-9.
  • Nitiss JL, Rose A, Sykes KC, Harris J, Zhou J. Using yeast to understand drugs that target topoisomerases.. Annals of the New York Academy of Sciences. 1996;803:32-43.
  • Nitiss JL, Wang JC. Mechanisms of cell killing by drugs that trap covalent complexes between DNA topoisomerases and DNA.. Molecular pharmacology. 1996;50(5):1095-102.
  • Nitiss JL, Beck WT. Antitopoisomerase drug action and resistance.. European journal of cancer (Oxford, England : 1990). 1996;32A(6):958-66.
  • Hsiung Y, Jannatipour M, Rose A, McMahon J, Duncan D, Nitiss JL. Functional expression of human topoisomerase II alpha in yeast: mutations at amino acids 450 or 803 of topoisomerase II alpha result in enzymes that can confer resistance to anti-topoisomerase II agents.. Cancer research. 1996;56(1):91-9.
  • Chang YC, Nair MG, Nitiss JL. Metabolites of daidzein and genistein and their biological activities.. Journal of natural products. 1995;58(12):1901-5.
  • Hsiung Y, Elsea SH, Osheroff N, Nitiss JL. A mutation in yeast TOP2 homologous to a quinolone-resistant mutation in bacteria. Mutation of the amino acid homologous to Ser83 of Escherichia coli gyrA alters sensitivity to eukaryotic topoisomerase inhibitors.. The Journal of biological chemistry. 1995;270(35):20359-64.
  • Ishida R, Hamatake M, Wasserman RA, Nitiss JL, Wang JC, Andoh T. DNA topoisomerase II is the molecular target of bisdioxopiperazine derivatives ICRF-159 and ICRF-193 in Saccharomyces cerevisiae.. Cancer research. 1995;55(11):2299-303.
  • Elsea SH, Hsiung Y, Nitiss JL, Osheroff N. A yeast type II topoisomerase selected for resistance to quinolones. Mutation of histidine 1012 to tyrosine confers resistance to nonintercalative drugs but hypersensitivity to ellipticine.. The Journal of biological chemistry. 1995;270(4):1913-20.
  • Nitiss JL, Vilalta PM, Wu H, McMahon J. Mutations in the gyrB domain of eukaryotic topoisomerase II can lead to partially dominant resistance to etoposide and amsacrine.. Molecular pharmacology. 1994;46(4):773-7.
  • , Hsiung Y, Jannatipour M, Yeh Y, Nitiss JL. Yeast topoisomerase II mutants resistant to anti-topoisomerase agents: identification and characterization of new yeast topoisomerase II mutants selected for resistance to etoposide.. Cancer research. 1994;54(11):2943-51.
  • Nitiss JL. Roles of DNA topoisomerases in chromosomal replication and segregation.. Advances in pharmacology (San Diego, Calif.). 1994;29A:103-34.
  • Nitiss JL. Using yeast to study resistance to topoisomerase II-targeting drugs.. Cancer chemotherapy and pharmacology. 1994;34 Suppl:S6-13.
  • Nitiss JL. Yeast as a genetic model system for studying topoisomerase inhibitors.. Advances in pharmacology (San Diego, Calif.). 1994;29B:201-26.
  • Jannatipour M, , Nitiss JL. The top2-5 mutant of yeast topoisomerase II encodes an enzyme resistant to etoposide and amsacrine.. The Journal of biological chemistry. 1993;268(25):18586-92.
  • Nitiss JL, , Hsiung Y. A temperature sensitive topoisomerase II allele confers temperature dependent drug resistance on amsacrine and etoposide: a genetic system for determining the targets of topoisomerase II inhibitors.. Cancer research. 1993;53(1):89-93.
  • Nitiss JL, , Harbury P, Jannatipour M, Wasserman R, Wang JC. Amsacrine and etoposide hypersensitivity of yeast cells overexpressing DNA topoisomerase II.. Cancer research. 1992;52(16):4467-72.
  • Elsea SH, Osheroff N, Nitiss JL. Cytotoxicity of quinolones toward eukaryotic cells. Identification of topoisomerase II as the primary cellular target for the quinolone CP-115,953 in yeast.. The Journal of biological chemistry. 1992;267(19):13150-3.