dna topoisomerases


Summary: Enzymes that regulate the topology of DNA by actions such as breaking, relaxing, passing, and rejoining strands of DNA in cells. These enzymes are important components of the DNA replication system. They are classified by their substrate specificities. DNA TOPOISOMERASE I enzymes act on a single strand of DNA. DNA TOPOISOMERASE II enzymes act on double strands of DNA.

Top Publications

  1. Nitiss J. DNA topoisomerases in cancer chemotherapy: using enzymes to generate selective DNA damage. Curr Opin Investig Drugs. 2002;3:1512-6 pubmed
    ..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. ..
  2. Shingu Y, Mikawa T, Onuma M, Hirayama T, Shibata T. A DNA-binding surface of SPO11-1, an Arabidopsis SPO11 orthologue required for normal meiosis. FEBS J. 2010;277:2360-74 pubmed publisher
    ..Thus, the Gly215, Arg222 and Arg223 residues of SPO11-1 form a DNA-binding surface that is functional in meiosis. ..
  3. Shinohara M, Shita Yamaguchi E, Buerstedde J, Shinagawa H, Ogawa H, Shinohara A. Characterization of the roles of the Saccharomyces cerevisiae RAD54 gene and a homologue of RAD54, RDH54/TID1, in mitosis and meiosis. Genetics. 1997;147:1545-56 pubmed
    ..These results suggest that one of the differences between the late stages of mitotic recombination and meiotic recombination might be specified by differential dependency on the Rad54 and Rdh54/Tid1 proteins. ..
  4. Holden J. DNA topoisomerases as anticancer drug targets: from the laboratory to the clinic. Curr Med Chem Anticancer Agents. 2001;1:1-25 pubmed
    b>DNA topoisomerases play important roles in basic cellular biology. Recently they have been identified as the molecular targets of a variety of pharmaceutical agents. Some of the drugs that target the topoisomerases are anticancer drugs...
  5. Chi P, Kwon Y, Seong C, Epshtein A, Lam I, Sung P, et al. Yeast recombination factor Rdh54 functionally interacts with the Rad51 recombinase and catalyzes Rad51 removal from DNA. J Biol Chem. 2006;281:26268-79 pubmed
    ..Rad51 complex formation. The Rdh54 expression and purification procedures described here should facilitate the functional dissection of this DNA recombination/repair factor. ..
  6. Klein H. RDH54, a RAD54 homologue in Saccharomyces cerevisiae, is required for mitotic diploid-specific recombination and repair and for meiosis. Genetics. 1997;147:1533-43 pubmed
    ..The role of the RDH54 gene in mitotic repair and in meiosis and the pathway in which it acts are discussed. ..
  7. Holzen T, Shah P, Olivares H, Bishop D. Tid1/Rdh54 promotes dissociation of Dmc1 from nonrecombinogenic sites on meiotic chromatin. Genes Dev. 2006;20:2593-604 pubmed
    ..The results raise the possibility that ATP hydrolysis-dependent disruption of nonproductive recombinase-DNA interactions is a feature shared with other homologous recombination systems. ..
  8. Prasad T, Robertson R, Visnapuu M, Chi P, Sung P, Greene E. A DNA-translocating Snf2 molecular motor: Saccharomyces cerevisiae Rdh54 displays processive translocation and extrudes DNA loops. J Mol Biol. 2007;369:940-53 pubmed
    ..Our work, together with other recent studies, suggests that translocation-coupled DNA loop extrusion is a common mechanistic feature among the Snf2-family of chromatin-remodeling proteins. ..
  9. Das B, Ganguly A, Majumder H. DNA topoisomerases of Leishmania: the potential targets for anti-leishmanial therapy. Adv Exp Med Biol. 2008;625:103-15 pubmed publisher
    ..This ancient eukaryote shows variable genetic diversity in their life cycle, wherein DNA topoisomerases play a key role in cellular processes affecting the topology and organization ofintracellular DNA...

More Information


  1. Petukhova G, Sung P, Klein H. Promotion of Rad51-dependent D-loop formation by yeast recombination factor Rdh54/Tid1. Genes Dev. 2000;14:2206-15 pubmed
    ..Efficient D-loop formation occurs with even topologically relaxed DNA, suggesting that via specific protein-protein interactions, the negative supercoils produced by Rdh54 are used by Rad51 for making DNA joints. ..
  2. Hartung F, Puchta H. Molecular characterization of homologues of both subunits A (SPO11) and B of the archaebacterial topoisomerase 6 in plants. Gene. 2001;271:81-6 pubmed
    ..Our data suggest that plants possess in contrast to other eukaryotes an additional archaebacterial kind of topoisomerase. ..
  3. Rui S, Tse Dinh Y. Topoisomerase function during bacterial responses to environmental challenge. Front Biosci. 2003;8:d256-63 pubmed
  4. Raoult D, Audic S, Robert C, Abergel C, Renesto P, Ogata H, et al. The 1.2-megabase genome sequence of Mimivirus. Science. 2004;306:1344-50 pubmed
    ..This new sequence data might help shed a new light on the origin of DNA viruses and their role in the early evolution of eukaryotes. ..
  5. Corbett K, Berger J. Structure, molecular mechanisms, and evolutionary relationships in DNA topoisomerases. Annu Rev Biophys Biomol Struct. 2004;33:95-118 pubmed
    ..A synthesis of these approaches has provided researchers with new physical insights into how topoisomerases employ chemistry and allostery to direct the large-scale molecular motions needed to pass DNA strands through each other. ..
  6. Stacey N, Kuromori T, Azumi Y, Roberts G, Breuer C, Wada T, et al. Arabidopsis SPO11-2 functions with SPO11-1 in meiotic recombination. Plant J. 2006;48:206-16 pubmed
    ..Thus, the three Arabidopsis Spo11 homologues appear to function in two discrete processes, i.e. AtSPO11-1 and AtSPO11-2 in meiotic recombination and AtSPO11-3 in DNA replication. ..
  7. Nadal M. Reverse gyrase: an insight into the role of DNA-topoisomerases. Biochimie. 2007;89:447-55 pubmed
    ..These data give us a new insight in the cellular role of reverse gyrase. Moreover, it has been proposed that reverse gyrase has been implicated in genome stability. ..
  8. Balsalobre L, Ferrándiz M, de Alba G, de la Campa A. Nonoptimal DNA topoisomerases allow maintenance of supercoiling levels and improve fitness of Streptococcus pneumoniae. Antimicrob Agents Chemother. 2011;55:1097-105 pubmed publisher
    ..An increase in the incidence of fluoroquinolone resistance, even in the absence of further antibiotic exposure, is envisaged. ..
  9. Lin J, Lu H, Lee J, Lin J, Hsia T, Wu L, et al. (-)-Menthol inhibits DNA topoisomerases I, II alpha and beta and promotes NF-kappaB expression in human gastric cancer SNU-5 cells. Anticancer Res. 2005;25:2069-74 pubmed
    ..These data suggest that (-)-Menthol may induce cytotoxicity through inhibiting gene expression of topoisomerase I, IIalpha and IIbeta and promoting the gene expression of NF-kappaB in SNU-5 cells. ..
  10. Kouzine F, Sanford S, Elisha Feil Z, Levens D. The functional response of upstream DNA to dynamic supercoiling in vivo. Nat Struct Mol Biol. 2008;15:146-54 pubmed publisher
    ..These results indicate that mechanical stresses, constrained by architectural features of DNA and chromatin, may broadly contribute to gene regulation. ..
  11. Russo P, Del Bufalo A, Cesario A. Flavonoids acting on DNA topoisomerases: recent advances and future perspectives in cancer therapy. Curr Med Chem. 2012;19:5287-93 pubmed
    ..Daidzein or its synthetic derivative Phenoxodiol as well as Luteolin and Quercetin are able to inhibit DNA topoisomerases. This review discusses that Flavonoids targeting DNA topoisomerases may lead to novel drug development with ..
  12. Bakshi R, Shapiro T. DNA topoisomerases as targets for antiprotozoal therapy. Mini Rev Med Chem. 2003;3:597-608 pubmed
    ..b>DNA topoisomerases are clinically relevant targets for anti-cancer and anti-bacterial agents...
  13. Klein H. Mutations in recombinational repair and in checkpoint control genes suppress the lethal combination of srs2Delta with other DNA repair genes in Saccharomyces cerevisiae. Genetics. 2001;157:557-65 pubmed
    ..However, cells do not achieve wild-type growth rates, suggesting that unrepaired damage is still present and may lead to chromosome loss. ..
  14. Signon L, Malkova A, Naylor M, Klein H, Haber J. Genetic requirements for RAD51- and RAD54-independent break-induced replication repair of a chromosomal double-strand break. Mol Cell Biol. 2001;21:2048-56 pubmed
    ..The similar genetic requirements for BIR and telomere maintenance in the absence of telomerase also suggest that these two processes proceed by similar mechanisms. ..
  15. Shah P, Zheng X, Epshtein A, Carey J, Bishop D, Klein H. Swi2/Snf2-related translocases prevent accumulation of toxic Rad51 complexes during mitotic growth. Mol Cell. 2010;39:862-72 pubmed publisher
  16. Cortés F, Pastor N, Mateos S, Dominguez I. Roles of DNA topoisomerases in chromosome segregation and mitosis. Mutat Res. 2003;543:59-66 pubmed
    b>DNA topoisomerases are highly specialized nuclear enzymes that perform topological changes in the DNA molecule in a very precise and unique fashion...
  17. Shinohara M, Gasior S, Bishop D, Shinohara A. Tid1/Rdh54 promotes colocalization of rad51 and dmc1 during meiotic recombination. Proc Natl Acad Sci U S A. 2000;97:10814-9 pubmed
  18. Nimonkar A, Amitani I, Baskin R, Kowalczykowski S. Single molecule imaging of Tid1/Rdh54, a Rad54 homolog that translocates on duplex DNA and can disrupt joint molecules. J Biol Chem. 2007;282:30776-84 pubmed
    ..The ability of Tid1 translocation to clear DNA of proteins and to migrate recombination intermediates may be of critical importance for DNA repair and chromosome dynamics. ..
  19. Schoeffler A, Berger J. DNA topoisomerases: harnessing and constraining energy to govern chromosome topology. Q Rev Biophys. 2008;41:41-101 pubmed publisher
    b>DNA topoisomerases are a diverse set of essential enzymes responsible for maintaining chromosomes in an appropriate topological state...
  20. Bermejo R, Katou Y, Shirahige K, Foiani M. ChIP-on-chip analysis of DNA topoisomerases. Methods Mol Biol. 2009;582:103-18 pubmed publisher
    ..By using this approach, novel aspects of DNA topoisomerase function in chromosome metabolism might be unmasked. ..
  21. Champoux J. DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem. 2001;70:369-413 pubmed
    b>DNA topoisomerases solve the topological problems associated with DNA replication, transcription, recombination, and chromatin remodeling by introducing temporary single- or double-strand breaks in the DNA...
  22. Miyagawa K, Tsuruga T, Kinomura A, Usui K, Katsura M, Tashiro S, et al. A role for RAD54B in homologous recombination in human cells. EMBO J. 2002;21:175-80 pubmed
    ..Our findings provide the first genetic evidence that the mitotic recombination pathway is functionally conserved from yeast to humans. ..
  23. Pedersen J, Fredsoe J, Roedgaard M, Andreasen L, Mundbjerg K, Kruhøffer M, et al. DNA Topoisomerases maintain promoters in a state competent for transcriptional activation in Saccharomyces cerevisiae. PLoS Genet. 2012;8:e1003128 pubmed publisher
    To investigate the role of DNA topoisomerases in transcription, we have studied global gene expression in Saccharomyces cerevisiae cells deficient for topoisomerases I and II and performed single-gene analyses to support our findings...
  24. Forterre P, Gadelle D. Phylogenomics of DNA topoisomerases: their origin and putative roles in the emergence of modern organisms. Nucleic Acids Res. 2009;37:679-92 pubmed publisher
    ..We also proposed that topoisomerases have played a critical role in the origin of modern genomes and in the emergence of the three cellular domains. ..
  25. Pommier Y, Leo E, Zhang H, Marchand C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem Biol. 2010;17:421-33 pubmed publisher
    b>DNA topoisomerases are the targets of important anticancer and antibacterial drugs...
  26. Ridley C, Reddy M, Rocha G, Bushman F, Faulkner D. Total synthesis and evaluation of lamellarin alpha 20-Sulfate analogues. Bioorg Med Chem. 2002;10:3285-90 pubmed
    ..Lamellarin alpha 13,20-disulfate is a moderate inhibitor of both HIV-1 integrase and cancer cell lines. Lamellarin H is a more potent inhibitor of HIV-1 integrase but lacked the specificity required to be medicinally useful. ..
  27. Park H, Kim Y, Kim J, Lee E, Yi Y, Hwang H, et al. 6-Arylamino-7-chloro-quinazoline-5,8-diones as novel cytotoxic and DNA topoisomerase inhibitory agents. Bioorg Med Chem Lett. 2004;14:3385-8 pubmed
    ..To further investigate the cytotoxic mechanism, the effects of test compounds on DNA topoisomerase I and II activities have been assessed. ..
    ..All of the compounds demonstrated activity against DNA topoisomerases II at the concentration 10 µM, but they did not inhibit activity of topoisomerase I...
  29. Yakovleva L, Handy C, Yagi H, Sayer J, Jerina D, Shuman S. Intercalating polycyclic aromatic hydrocarbon-DNA adducts poison DNA religation by Vaccinia topoisomerase and act as roadblocks to digestion by exonuclease III. Biochemistry. 2006;45:7644-53 pubmed
    ..These results highlight the sensitivity of repair outcomes to the structure of the PAH ring system and whether intercalation occurs via the major or minor groove. ..
  30. Liu J, Sondheimer N, Lindquist S. Changes in the middle region of Sup35 profoundly alter the nature of epigenetic inheritance for the yeast prion [PSI+]. Proc Natl Acad Sci U S A. 2002;99 Suppl 4:16446-53 pubmed
  31. Vogel C, Kienitz A, Muller R, Bastians H. The mitotic spindle checkpoint is a critical determinant for topoisomerase-based chemotherapy. J Biol Chem. 2005;280:4025-8 pubmed
    ..Its frequent inactivation in human cancer might contribute to the observed resistance of tumor cells to these chemotherapeutic drugs. ..
  32. Mizushina Y, Murakami C, Takikawa H, Kasai N, Xu X, Mori K, et al. Molecular action mode of Hippospongic acid A, an inhibitor of gastrulation of starfish embryos. J Biochem. 2003;133:541-52 pubmed
    ..9-17.6 microM, and interestingly also those of human DNA topoisomerases I and II (IC(50) = 15-25 microM)...
  33. Pućkowska A, Bielawski K, Bielawska A, Rózański A. New carbocyclic analogues of netropsin: synthesis and inhibition of topoisomerases. Acta Biochim Pol. 2002;49:177-83 pubmed
    ..Compounds 4-7 consist of two netropsin-like units linked by aliphatic (tetra- and hexamethylene) chains. In the topoisomerase I and II assay, the relaxation of pBR322 plasmid was inhibited by compounds 4-7 at 100 microM concentration. ..
  34. Vos S, Tretter E, Schmidt B, Berger J. All tangled up: how cells direct, manage and exploit topoisomerase function. Nat Rev Mol Cell Biol. 2011;12:827-41 pubmed publisher
    ..Despite decades of study, surprising findings involving topoisomerases continue to emerge with respect to their cellular function, regulation and utility as therapeutic targets. ..
  35. Capranico G, Zagotto G, Palumbo M. Development of DNA topoisomerase-related therapeutics: a short perspective of new challenges. Curr Med Chem Anticancer Agents. 2004;4:335-45 pubmed
    ..b>DNA topoisomerases remain the most significant target of these cytotoxic drugs and constitute a growing family of nuclear ..
  36. Descloux S, Rossano A, Perreten V. Characterization of new staphylococcal cassette chromosome mec (SCCmec) and topoisomerase genes in fluoroquinolone- and methicillin-resistant Staphylococcus pseudintermedius. J Clin Microbiol. 2008;46:1818-23 pubmed publisher
    ..Analysis of the complete nucleotide sequences of the topoisomerase loci gyrB/gyrA and grlB/grlA revealed mutations involved in fluoroquinolone resistance. ..
  37. Zhang X, Goeres J, Zhang H, Yen T, Porter A, Matunis M. SUMO-2/3 modification and binding regulate the association of CENP-E with kinetochores and progression through mitosis. Mol Cell. 2008;29:729-41 pubmed publisher
    ..Our findings indicate that SUMOylation is a key regulator of the mammalian cell cycle, with SUMO-1 and SUMO-2/3 modification of different proteins regulating distinct processes. ..
  38. Rushton L, Sass A, Baldwin A, Dowson C, Donoghue D, Mahenthiralingam E. Key role for efflux in the preservative susceptibility and adaptive resistance of Burkholderia cepacia complex bacteria. Antimicrob Agents Chemother. 2013;57:2972-80 pubmed publisher
    ..In summary, intrinsic preservative tolerance and stable adaptive changes, such as enhanced efflux, play a role in the ability of Bcc bacteria to cause industrial contamination...
  39. Hwang J, Marshall J, Rizvi N. Combined inhibition of topoisomerases: a phase I. Study of irinotecan and epirubicin. Oncology (Williston Park). 2003;17:46-51 pubmed
    ..Other toxicities were acceptable and non-dose-limiting. Accrual of patients continues, at level 3A (irinotecan at 75 mg/m2, epirubicin at 25 mg/m2). ..
  40. Guterres Z, da Silva A, Garcez W, Garcez F, Fernandes C, Garcez F. Mutagenicity and recombinagenicity of Ocotea acutifolia (Lauraceae) aporphinoid alkaloids. Mutat Res. 2013;757:91-6 pubmed publisher
    ..its less-planar analogues 3 and 4. As previously reported for (+)-dicentrine (2), alkaloids 1, 3, and 4 may also be DNA intercalating agents, interfering with the catalytic activity of topoisomerases. ..
  41. Nagle A, Hur W, Gray N. Antimitotic agents of natural origin. Curr Drug Targets. 2006;7:305-26 pubmed
    ..Focus has been placed on agents that act directly on the mitotic machinery rather than on targets further upstream such as growth factor receptors. ..
  42. Mizushina Y, Tsuzuki T, Eitsuka T, Miyazawa T, Kobayashi K, Ikawa H, et al. Inhibitory action of conjugated C18-fatty acids on DNA polymerases and DNA topoisomerases. Lipids. 2004;39:977-83 pubmed
    ..as linoleic acid (18:2delta9c,12c) could potently inhibit the activities of mammalian DNA polymerases and DNA topoisomerases, but their saturated forms could not...
  43. Kang C, Li Y, Cherian J, Liu B, Ng H, Lee M, et al. Biophysical Studies of Bacterial Topoisomerases Substantiate Their Binding Modes to an Inhibitor. Biophys J. 2015;109:1969-77 pubmed publisher
    Bacterial DNA topoisomerases are essential for bacterial growth and are attractive, important targets for developing antibacterial drugs. Consequently, different potent inhibitors that target bacterial topoisomerases have been developed...
  44. Bellando Randone S, Guiducci S, Matucci Cerinic M. Very early diagnosis of systemic sclerosis. Pol Arch Med Wewn. 2012;122 Suppl 1:18-23 pubmed
    ..Although patients with RP, autoantibodies, and SSc capillaroscopic pattern could be easily followed up, there is still no agreement on the predictors that may allow us to identify patients who will develop an established disease. ..
  45. Wang J, Assassi S, Guo G, Tu W, Wu W, Yang L, et al. Clinical and serological features of systemic sclerosis in a Chinese cohort. Clin Rheumatol. 2013;32:617-21 pubmed publisher
    ..Clinical subtypes and the frequencies of SSc-related autoantibodies in Chinese SSc patients are significantly different from those in SSc patients of the US Caucasian descent. ..
  46. Leandro de Jesus T, Calderano S, Vitorino F, Llanos R, Lopes M, de Araújo C, et al. Quantitative Proteomic Analysis of Replicative and Nonreplicative Forms Reveals Important Insights into Chromatin Biology of Trypanosoma cruzi. Mol Cell Proteomics. 2017;16:23-38 pubmed publisher
    ..Proteins associated to DNA proliferation, such as PCNA, RPA, and DNA topoisomerases were exclusively found in the chromatin of replicative stages...
  47. Takeshita A. [Recent advances in the treatment of acute myelogenous leukemia: a view of the new agents]. Rinsho Ketsueki. 2003;44:1133-43 pubmed
  48. Espeli O, Marians K. Untangling intracellular DNA topology. Mol Microbiol. 2004;52:925-31 pubmed
  49. Lehmann M, Vilar K, Franco A, Reguly M, Rodrigues de Andrade H. Activity of topoisomerase inhibitors daunorubicin, idarubicin, and aclarubicin in the Drosophila Somatic Mutation and Recombination Test. Environ Mol Mutagen. 2004;43:250-7 pubmed
    ..This dual topo I and II inhibitory effect, associated with its DNA-intercalating activity, could contribute to the activity of ACLA in the SMART assay. ..
  50. Liu Z, Zechiedrich E, Chan H. Inferring global topology from local juxtaposition geometry: interlinking polymer rings and ramifications for topoisomerase action. Biophys J. 2006;90:2344-55 pubmed
    ..statistical mechanical principles emerging from these findings suggest that it is physically possible for DNA topoisomerases to decatenate effectively by acting selectively on juxtapositions with specific "hooked" ..
  51. Vrana J, Bieszczad C, Cleaveland E, Ma Y, Park J, Mohandas T, et al. An MCL1-overexpressing Burkitt lymphoma subline exhibits enhanced survival on exposure to serum deprivation, topoisomerase inhibitors, or staurosporine but remains sensitive to 1-beta-D-arabinofuranosylcytosine. Cancer Res. 2002;62:892-900 pubmed
  52. Morgan Linnell S, Zechiedrich L. Contributions of the combined effects of topoisomerase mutations toward fluoroquinolone resistance in Escherichia coli. Antimicrob Agents Chemother. 2007;51:4205-8 pubmed
    ..Strains with double mutations in both gyrA and parC had even higher MICs of fluoroquinolones than strains with totals of three mutations. ..
  53. Reinhardt A, Kempf I, Kobisch M, Gautier Bouchardon A. Fluoroquinolone resistance in Mycoplasma gallisepticum: DNA gyrase as primary target of enrofloxacin and impact of mutations in topoisomerases on resistance level. J Antimicrob Chemother. 2002;50:589-92 pubmed
    ..The results obtained also suggest that the preferential target of enrofloxacin in M. gallisepticum is DNA gyrase. ..
  54. Chosson E, Guguen Guillouzo C, Glaise D, Picot L, Seguin E, Besson T. Cytotoxic evaluation of sarcodifurines A and B, two novel dihydrofuroquinolines from Sarcomelicope follicularis (Rutaceae). J Enzyme Inhib Med Chem. 2008;23:704-7 pubmed
    ..In spite of the weak activity of sarcodifurines and furoquinolines, rationalized pharmacomodulations to obtain planar analogs could lead to efficient topoisomerases inhibitors and DNA intercalants. ..
  55. Levene S. Analysis of DNA topoisomers, knots, and catenanes by agarose gel electrophoresis. Methods Mol Biol. 2009;582:11-25 pubmed publisher
  56. Solier S, De Cian M, Bettaieb A, Desoche L, Solary E, Corcos L. PKC zeta controls DNA topoisomerase-dependent human caspase-2 pre-mRNA splicing. FEBS Lett. 2008;582:372-8 pubmed publisher
    ..Hence, the control of caspase-2 exon 9 inclusion by topoisomerase inhibitors depends on phosphorylation and/or dephosphorylation events, and on the cell cycle phase. ..
  57. Ishar M, Singh G, Singh S, Sreenivasan K, Singh G. Design, synthesis, and evaluation of novel 6-chloro-/fluorochromone derivatives as potential topoisomerase inhibitor anticancer agents. Bioorg Med Chem Lett. 2006;16:1366-70 pubmed
    ..The compounds displayed promising anticancer activity under these test systems and shall serve as useful 'leads' for further design...
  58. Santini C, Pellei M, Gandin V, Porchia M, Tisato F, Marzano C. Advances in copper complexes as anticancer agents. Chem Rev. 2014;114:815-62 pubmed publisher
  59. Rao V. Iron chelators with topoisomerase-inhibitory activity and their anticancer applications. Antioxid Redox Signal. 2013;18:930-55 pubmed publisher
    ..The commonalities and caveats of dual inhibition are presented in this review. Gaps in knowledge, relevant biomarkers, and strategies for future in vivo studies with dual inhibitors are discussed. ..
  60. Jain M, Tyagi A, Khurana J. Constitutive expression of a meiotic recombination protein gene homolog, OsTOP6A1, from rice confers abiotic stress tolerance in transgenic Arabidopsis plants. Plant Cell Rep. 2008;27:767-78 pubmed
  61. Majumder P, Pradhan S, Devi P, Pal S, Dasgupta D. Chromatin as a target for the DNA-binding anticancer drugs. Subcell Biochem. 2007;41:145-89 pubmed
    ..An overview will be given about the latest understanding of the molecular basis of their action. We shall restrict to those drugs, synthetic or natural, whose prime cellular targets are so far known to be chromosomal DNA. ..
  62. Ravanel N, Gestin B, Maurin M. In vitro selection of fluoroquinolone resistance in Brucella melitensis. Int J Antimicrob Agents. 2009;34:76-81 pubmed publisher
    ..In B. melitensis, fluoroquinolone resistance may arise from gyrA mutation and efflux pump overexpression mechanisms. ..
  63. Thompson K, Wang Y, Madej T, Bryant S. Improving protein structure similarity searches using domain boundaries based on conserved sequence information. BMC Struct Biol. 2009;9:33 pubmed publisher
    ..Because of the improvement in performance of structure similarity searches using sequence domain boundaries, we are in the process of implementing their inclusion into the VAST search and MMDB resources in the NCBI Entrez system. ..
  64. Cline S, Hanawalt P. Topoisomerase deficiencies subtly enhance global genomic repair of ultraviolet-induced DNA damage in Saccharomyces cerevisiae. DNA Repair (Amst). 2006;5:611-7 pubmed
    ..DNA repair mechanisms prevent mutations and aberrant recombination events by removing DNA damage. DNA topoisomerases maintain favorable nucleic acid topology for replication, transcription, and chromosome segregation...
  65. Shinohara M, Sakai K, Shinohara A, Bishop D. Crossover interference in Saccharomyces cerevisiae requires a TID1/RDH54- and DMC1-dependent pathway. Genetics. 2003;163:1273-86 pubmed
    ..These results support the proposal that crossover interference acts at the strand invasion stage of recombination. ..
  66. Sobolevsky Y, Trifonov E. Protein modules conserved since LUCA. J Mol Evol. 2006;63:622-34 pubmed
    ..The data presented, thus, make a basis for further developments toward the earliest stages of protein evolution. ..
  67. Macinga D, Renick P, Makin K, Ellis D, Kreiner A, Li M, et al. Unique biological properties and molecular mechanism of 5,6-bridged quinolones. Antimicrob Agents Chemother. 2003;47:2526-37 pubmed
    ..These results demonstrate that the 5,6-bridged quinolones act via a mechanism that is related to but qualitatively different from that of typical quinolones. ..
  68. Richter S, Cartei G, Nadai M, Trestin A, Barzon L, Palumbo M, et al. In vitro basis for schedule-dependent interaction between gemcitabine and topoisomerase-targeted drugs in the treatment of colorectal cancer. Ann Oncol. 2006;17 Suppl 5:v20-24 pubmed
    ..These findings help explaining the effectiveness of the combined therapy GEM/topoisomerase poisons and suggest a drug administration protocol for clinical treatment. ..
  69. Kozoderović G, Velhner M, Jelesić Z, Golic N, Lozo J, Kehrenberg C. Prevalence of quinolone resistance and mutations in the topoisomerase genes in Salmonella enterica serotype Enteritidis isolates from Serbia. Int J Antimicrob Agents. 2012;40:455-7 pubmed publisher
    ..No mutations were present in the gyrB, parC or parE genes. Although CIP resistance was absent, reduced susceptibility characterised by mutations in gyrA was apparent among S. Enteritidis isolates from Serbia. ..
  70. Anachkova B, Djeliova V, Russev G. Nuclear matrix support of DNA replication. J Cell Biochem. 2005;96:951-61 pubmed
  71. Kurose A, Tanaka T, Huang X, Halicka H, Traganos F, Dai W, et al. Assessment of ATM phosphorylation on Ser-1981 induced by DNA topoisomerase I and II inhibitors in relation to Ser-139-histone H2AX phosphorylation, cell cycle phase, and apoptosis. Cytometry A. 2005;68:1-9 pubmed
  72. Tumiatti V, Milelli A, Minarini A, Micco M, Gasperi Campani A, Roncuzzi L, et al. Design, synthesis, and biological evaluation of substituted naphthalene imides and diimides as anticancer agent. J Med Chem. 2009;52:7873-7 pubmed publisher
    ..Furthermore, 1 and 2 caused a decrease of ERK1/2 and, unlike mitonafide, inhibited ERKs phosphorylation. ..
  73. Feng L, Sha R, Seeman N, Chaikin P. Topological interaction by entangled DNA loops. Phys Rev Lett. 2012;109:188301 pubmed
    ..This novel topological interaction may lead to new materials and phenomena such as particles strung on necklaces, confined motions on designed contours and surfaces, and colloidal Olympic gels. ..
  74. Biroccio A, Benassi B, Fiorentino F, Zupi G. Glutathione depletion induced by c-Myc downregulation triggers apoptosis on treatment with alkylating agents. Neoplasia. 2004;6:195-206 pubmed
    ..All together, these results demonstrate that GSH plays a key role in governing c-Myc-dependent drug-induced apoptosis. ..
  75. Roca J. Two-dimensional agarose gel electrophoresis of DNA topoisomers. Methods Mol Biol. 2009;582:27-37 pubmed publisher
    ..These compounds alter the overall shape of the DNA and, thereby, change the relative mobility of individual DNA topoisomers. ..
  76. Wang B, Perchellet E, Wang Y, Tamura M, Hua D, Perchellet J. Antitumor triptycene bisquinones: a novel synthetic class of dual inhibitors of DNA topoisomerase I and II activities. Anticancer Drugs. 2003;14:503-14 pubmed
    ..Because of their ability to target nucleoside transport and topoisomerase activities, synthetic TT bisquinones might represent a novel class of bifunctional drugs valuable to develop new means of polychemotherapy and circumvent MDR. ..
  77. Odds F. Genomics, molecular targets and the discovery of antifungal drugs. Rev Iberoam Micol. 2005;22:229-37 pubmed
  78. Fan J, Huang T, Wen C, Shen T, Li T. Sodium salicylate acts through direct inhibition of phosphoinositide 3-kinase-like kinases to modulate topoisomerase-mediated DNA damage responses. Eur J Pharmacol. 2010;638:13-20 pubmed publisher
    ..Together, our study provides evidence that NSAIDs exhibit a novel COX-independent modulating activity of NSAIDs on the DNA damage responses and it is through inhibition of phosphoinositide 3-kinase-like kinases. ..