PDBsum entry 1a36

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protein dna_rna links
Isomerase/DNA PDB id
Protein chain
544 a.a. *
Waters ×57
* Residue conservation analysis
PDB id:
Name: Isomerase/DNA
Title: Topoisomerase i/DNA complex
Structure: DNA (5'- d( Ap Ap Ap Ap Ap Gp Ap Cp Tp Tp Ap Gp Ap Ap Ap Ap A p Tp Tp Tp Tp T)- 3'). Chain: b. Engineered: yes. DNA (5'- d( Ap Ap Ap Ap Ap Tp Tp Tp Tp Tp Cp Tp Ap Ap Gp Tp C p Tp Tp Tp Tp T)- 3'). Chain: c.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: nucleus. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Biol. unit: Monomer (from PDB file)
2.80Å     R-factor:   0.224     R-free:   0.312
Authors: L.Stewart,M.R.Redinbo,X.Qiu,J.J.Champoux,W.G.J.Hol
Key ref:
L.Stewart et al. (1998). A model for the mechanism of human topoisomerase I. Science, 279, 1534-1541. PubMed id: 9488652 DOI: 10.1126/science.279.5356.1534
29-Jan-98     Release date:   12-Aug-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P11387  (TOP1_HUMAN) -  DNA topoisomerase 1
765 a.a.
544 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Dna topoisomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     chromosome   1 term 
  Biological process     DNA topological change   1 term 
  Biochemical function     DNA binding     3 terms  


DOI no: 10.1126/science.279.5356.1534 Science 279:1534-1541 (1998)
PubMed id: 9488652  
A model for the mechanism of human topoisomerase I.
L.Stewart, M.R.Redinbo, X.Qiu, W.G.Hol, J.J.Champoux.
The three-dimensional structure of a 70-kilodalton amino terminally truncated form of human topoisomerase I in complex with a 22-base pair duplex oligonucleotide, determined to a resolution of 2.8 angstroms, reveals all of the structural elements of the enzyme that contact DNA. The linker region that connects the central core of the enzyme to the carboxyl-terminal domain assumes a coiled-coil configuration and protrudes away from the remainder of the enzyme. The positively charged DNA-proximal surface of the linker makes only a few contacts with the DNA downstream of the cleavage site. In combination with the crystal structures of the reconstituted human topoisomerase I before and after DNA cleavage, this information suggests which amino acid residues are involved in catalyzing phosphodiester bond breakage and religation. The structures also lead to the proposal that the topoisomerization step occurs by a mechanism termed "controlled rotation."
  Selected figure(s)  
Figure 1.
Fig. 1. Structure of the linker region of 70-kD human topo I. (A) Stereoview of the linker domain (Ser643 to Arg708) of human topo I (linker, orange, C trace) structurally aligned^ with a variant of the coiled-coil of E. coli repressor of primer (Rop<2aa>, black, C trace) (11). The side chains that form the hydrophobic interface of each coiled-coil are also shown for the linker (orange) and Rop<2aa> (cyan). (B) Cutaway view of a three-helix sheet formed by hydrophobic interactions between the linker domain helices ( 18 and 19) and helix 17 of core subdomain III as seen in topo70. Helix 20 of the COOH-terminal domain is in green. All side chains that engage in hydrophobic interactions in the three-helix sheet are in gray and labeled according to their domain designation as linker (orange) or core subdomain III (red). Active site residues His632 and Phe^723 are also shown. (C) Structure-based sequence alignment of E. coli Rop<2aa> (11) (accession number P03051), the E. coli transcript cleavage factor GreA (29) (accession number X54718), and the linker domain of human topo I (30). The^ pairwise hydrophobic and salt bridge interactions that stabilize^ the coiled-coil of the human linker are represented by numbers in gray or colored boxes, respectively. Side chain properties are represented with colored boxes: cyan for polar, green for positive charge, red for negative charge, and gray for hydrophobic. DNA contacts made by the human residues Arg650 and Lys708 are indicated with light blue boxes. Residues with side chains on the top (DNA proximal), side, and bottom surfaces of the coil-coiled^ are indicated with colored boxes, and the surface charge ratios are on the right.
Figure 4.
Fig. 4. The controlled rotation mechanism of human topo I. The highly negatively superhelical substrate DNA (red with right handed^ writhe) becomes partially relaxed through steps (A) through (G) and is converted to the less supercoiled state depicted^ in green. Human topo I (topo70) is rendered as a bilobed structure^ with core subdomains I and II forming the "cap" lobe (cyan), and^ core subdomain III plus the COOH-terminal and linker domains forming the "catalytic" lobe (magenta). The structure shown in (D) is expanded by a factor of 2 and shows the C trace of the protein with the rotating DNA depicted as a series of different-colored^ rotation states that show the DNA segment at 30° intervals. Because^ the shape of the enzyme is complementary to but not always in direct contact with the surface of the substrate DNA, small rocking movements (small arrows) may be allowed during the events of controlled^ rotation.
  The above figures are reprinted by permission from the AAAs: Science (1998, 279, 1534-1541) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20855291 A.C.Gentry, S.Juul, C.Veigaard, B.R.Knudsen, and N.Osheroff (2011).
The geometry of DNA supercoils modulates the DNA cleavage activity of human topoisomerase I.
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21132352 O.M.Koo, I.Rubinstein, and H.Onyüksel (2011).
Actively targeted low-dose camptothecin as a safe, long-acting, disease-modifying nanomedicine for rheumatoid arthritis.
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22108601 S.M.Vos, E.M.Tretter, B.H.Schmidt, and J.M.Berger (2011).
All tangled up: how cells direct, manage and exploit topoisomerase function.
  Nat Rev Mol Cell Biol, 12, 827-841.  
21186185 S.Sengupta, A.Ganguly, A.Roy, S.Bosedasgupta, I.D'Annessa, A.Desideri, and H.K.Majumder (2011).
ATP independent type IB topoisomerase of Leishmania donovani is stimulated by ATP: an insight into the functional mechanism.
  Nucleic Acids Res, 39, 3295-3309.  
21504738 T.D.Lillian, M.Taranova, J.Wereszczynski, I.Andricioaei, and N.C.Perkins (2011).
A multiscale dynamic model of DNA supercoil relaxation by topoisomerase IB.
  Biophys J, 100, 2016-2023.  
21482796 Z.Zhang, B.Cheng, and Y.C.Tse-Dinh (2011).
Crystal structure of a covalent intermediate in DNA cleavage and rejoining by Escherichia coli DNA topoisomerase I.
  Proc Natl Acad Sci U S A, 108, 6939-6944.  
20200034 C.García-Estrada, C.F.Prada, C.Fernández-Rubio, F.Rojo-Vázquez, and R.Balaña-Fouce (2010).
DNA topoisomerases in apicomplexan parasites: promising targets for drug discovery.
  Proc Biol Sci, 277, 1777-1787.  
19883377 C.Tesauro, P.Fiorani, I.D'Annessa, G.Chillemi, G.Turchi, and A.Desideri (2010).
Erybraedin C, a natural compound from the plant Bituminaria bituminosa, inhibits both the cleavage and religation activities of human topoisomerase I.
  Biochem J, 425, 531-539.  
20723754 D.A.Koster, A.Crut, S.Shuman, M.A.Bjornsti, and N.H.Dekker (2010).
Cellular strategies for regulating DNA supercoiling: a single-molecule perspective.
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20532182 G.Mancini, I.D'Annessa, A.Coletta, N.Sanna, G.Chillemi, and A.Desideri (2010).
Structural and dynamical effects induced by the anticancer drug topotecan on the human topoisomerase I - DNA complex.
  PLoS One, 5, e10934.  
20238115 H.Iwasaki, T.Okabe, K.Takara, Y.Yoshida, K.Hanashiro, and H.Oku (2010).
Down-regulation of lipids transporter ABCA1 increases the cytotoxicity of nitidine.
  Cancer Chemother Pharmacol, 66, 953-959.  
20308575 J.Wu, L.Feng, and T.S.Hsieh (2010).
Drosophila topo IIIalpha is required for the maintenance of mitochondrial genome and male germ-line stem cells.
  Proc Natl Acad Sci U S A, 107, 6228-6233.  
20152159 K.Perry, Y.Hwang, F.D.Bushman, and G.D.Van Duyne (2010).
Insights from the structure of a smallpox virus topoisomerase-DNA transition state mimic.
  Structure, 18, 127-137.
PDB code: 3igc
20187656 M.R.Stahley, and J.T.Stivers (2010).
Mechanism and specificity of DNA strand exchange catalyzed by vaccinia DNA topoisomerase type I.
  Biochemistry, 49, 2786-2795.  
20637419 R.Rajan, B.Taneja, and A.Mondragón (2010).
Structures of minimal catalytic fragments of topoisomerase V reveals conformational changes relevant for DNA binding.
  Structure, 18, 829-838.
PDB codes: 3m6k 3m6z 3m7d 3m7g
20603643 T.H.Huang, H.C.Chen, S.M.Chou, Y.C.Yang, J.R.Fan, and T.K.Li (2010).
Cellular processing determinants for the activation of damage signals in response to topoisomerase I-linked DNA breakage.
  Cell Res, 20, 1060-1075.  
19472416 C.Punchihewa, M.Carver, and D.Yang (2009).
DNA sequence selectivity of human topoisomerase I-mediated DNA cleavage induced by camptothecin.
  Protein Sci, 18, 1326-1331.  
19551725 L.Shuai, S.Wang, L.Zhang, B.Fu, and X.Zhou (2009).
Cationic porphyrins and analogues as new DNA topoisomerase I and II inhibitors.
  Chem Biodivers, 6, 827-837.  
19194512 L.Vernis, C.Facca, E.Delagoutte, N.Soler, R.Chanet, B.Guiard, G.Faye, and G.Baldacci (2009).
A newly identified essential complex, Dre2-Tah18, controls mitochondria integrity and cell death after oxidative stress in yeast.
  PLoS ONE, 4, e4376.  
19151088 la Loza, and R.E.Wellinger (2009).
A novel approach for organelle-specific DNA damage targeting reveals different susceptibility of mitochondrial DNA to the anticancer drugs camptothecin and topotecan.
  Nucleic Acids Res, 37, e26.  
19106140 N.M.Baker, R.Rajan, and A.Mondragón (2009).
Structural studies of type I topoisomerases.
  Nucleic Acids Res, 37, 693-701.  
19083133 N.Tsavaris, A.Lazaris, C.Kosmas, P.Gouveris, N.Kavantzas, P.Kopterides, T.Papathomas, G.Agrogiannis, G.Arapogiannis, H.Zorzos, V.Kyriakou, E.Patsouris, and E.Patsouris (2009).
Topoisomerase I and IIalpha protein expression in primary colorectal cancer and recurrences following 5-fluorouracil-based adjuvant chemotherapy.
  Cancer Chemother Pharmacol, 64, 391-398.  
19452556 O.Szklarczyk, K.StaroĊ„, and M.Cieplak (2009).
Native state dynamics and mechanical properties of human topoisomerase I within a structure-based coarse-grained model.
  Proteins, 77, 420-431.  
19767617 P.Fiorani, C.Tesauro, G.Mancini, G.Chillemi, I.D'Annessa, G.Graziani, L.Tentori, A.Muzi, and A.Desideri (2009).
Evidence of the crucial role of the linker domain on the catalytic activity of human topoisomerase I by experimental and simulative characterization of the Lys681Ala mutant.
  Nucleic Acids Res, 37, 6849-6858.  
20161688 S.M.Aris, and N.P.Farrell (2009).
Towards Antitumor Active trans-Platinum Compounds.
  Eur J Inorg Chem, 2009, 1293.  
19476377 Y.Pommier (2009).
DNA topoisomerase I inhibitors: chemistry, biology, and interfacial inhibition.
  Chem Rev, 109, 2894-2902.  
19740104 Z.Yang, J.F.Carey, and J.J.Champoux (2009).
Mutational analysis of the preferential binding of human topoisomerase I to supercoiled DNA.
  FEBS J, 276, 5906-5919.  
18755053 A.J.Schoeffler, and J.M.Berger (2008).
DNA topoisomerases: harnessing and constraining energy to govern chromosome topology.
  Q Rev Biophys, 41, 41.  
18772225 C.Losasso, E.Cretaio, P.Fiorani, I.D'Annessa, G.Chillemi, and P.Benedetti (2008).
A single mutation in the 729 residue modulates human DNA topoisomerase IB DNA binding and drug resistance.
  Nucleic Acids Res, 36, 5635-5644.  
18292117 D.A.Koster, F.Czerwinski, L.Halby, A.Crut, P.Vekhoff, K.Palle, P.B.Arimondo, and N.H.Dekker (2008).
Single-molecule observations of topotecan-mediated TopIB activity at a unique DNA sequence.
  Nucleic Acids Res, 36, 2301-2310.  
18157856 F.Animati, M.Berettoni, M.Bigioni, M.Binaschi, P.Felicetti, L.Gontrani, O.Incani, A.Madami, E.Monteagudo, L.Olivieri, S.Resta, C.Rossi, and A.Cipollone (2008).
Synthesis, biological evaluation, and molecular modeling studies of rebeccamycin analogues modified in the carbohydrate moiety.
  ChemMedChem, 3, 266-279.  
18765473 G.Chillemi, I.D'Annessa, P.Fiorani, C.Losasso, P.Benedetti, and A.Desideri (2008).
Thr729 in human topoisomerase I modulates anti-cancer drug resistance by altering protein domain communications as suggested by molecular dynamics simulations.
  Nucleic Acids Res, 36, 5645-5651.  
18215123 G.S.Laco, and Y.Pommier (2008).
Role of a tryptophan anchor in human topoisomerase I structure, function and inhibition.
  Biochem J, 411, 523-530.  
18508107 H.Kim, J.H.Cardellina, R.Akee, J.J.Champoux, and J.T.Stivers (2008).
Arylstibonic acids: novel inhibitors and activators of human topoisomerase IB.
  Bioorg Chem, 36, 190-197.  
18693244 K.Palle, L.Pattarello, M.van der Merwe, C.Losasso, P.Benedetti, and M.A.Bjornsti (2008).
Disulfide cross-links reveal conserved features of DNA topoisomerase I architecture and a role for the N terminus in clamp closure.
  J Biol Chem, 283, 27767-27775.  
18443285 S.Sirikantaramas, M.Yamazaki, and K.Saito (2008).
Mutations in topoisomerase I as a self-resistance mechanism coevolved with the production of the anticancer alkaloid camptothecin in plants.
  Proc Natl Acad Sci U S A, 105, 6782-6786.  
18927559 T.S.Dexheimer, and Y.Pommier (2008).
DNA cleavage assay for the identification of topoisomerase I inhibitors.
  Nat Protoc, 3, 1736-1750.  
17804808 B.Taneja, B.Schnurr, A.Slesarev, J.F.Marko, and A.Mondragón (2007).
Topoisomerase V relaxes supercoiled DNA by a constrained swiveling mechanism.
  Proc Natl Acad Sci U S A, 104, 14670-14675.  
17367810 C.H.Ma, A.Kwiatek, S.Bolusani, Y.Voziyanov, and M.Jayaram (2007).
Unveiling hidden catalytic contributions of the conserved His/Trp-III in tyrosine recombinases: assembly of a novel active site in Flp recombinase harboring alanine at this position.
  J Mol Biol, 368, 183-196.  
17434318 C.Punchihewa, J.Dai, M.Carver, and D.Yang (2007).
Human topoisomerase I C-terminal domain fragment containing the active site tyrosine is a molten globule: implication for the formation of competent productive complex.
  J Struct Biol, 159, 111-121.  
17439970 G.Chillemi, A.Bruselles, P.Fiorani, S.Bueno, and A.Desideri (2007).
The open state of human topoisomerase I as probed by molecular dynamics simulation.
  Nucleic Acids Res, 35, 3032-3038.  
17889664 H.Aihara, W.M.Huang, and T.Ellenberger (2007).
An interlocked dimer of the protelomerase TelK distorts DNA structure for the formation of hairpin telomeres.
  Mol Cell, 27, 901-913.
PDB code: 2v6e
18022919 L.Liqing, G.Lin, S.Ming, and S.Hanwen (2007).
Determination of hydroxycamptothecinum by flow injection analysis with chemiluminescence detection.
  J Clin Lab Anal, 21, 356-362.  
17605046 P.Gouveris, A.C.Lazaris, T.G.Papathomas, A.Nonni, V.Kyriakou, J.Delladetsima, E.S.Patsouris, and N.Tsavaris (2007).
Topoisomerase I protein expression in primary colorectal cancer and recurrences after 5-FU-based adjuvant chemotherapy.
  J Cancer Res Clin Oncol, 133, 1011-1015.  
17827209 R.F.Frøhlich, C.Veigaard, F.F.Andersen, A.K.McClendon, A.C.Gentry, A.H.Andersen, N.Osheroff, T.Stevnsner, and B.R.Knudsen (2007).
Tryptophane-205 of human topoisomerase I is essential for camptothecin inhibition of negative but not positive supercoil removal.
  Nucleic Acids Res, 35, 6170-6180.  
16505102 C.Marchand, S.Antony, K.W.Kohn, M.Cushman, A.Ioanoviciu, B.L.Staker, A.B.Burgin, L.Stewart, and Y.Pommier (2006).
A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex.
  Mol Cancer Ther, 5, 287-295.  
16710299 J.Salceda, X.Fernández, and J.Roca (2006).
Topoisomerase II, not topoisomerase I, is the proficient relaxase of nucleosomal DNA.
  EMBO J, 25, 2575-2583.  
16895336 J.T.Stivers, and R.Nagarajan (2006).
Probing enzyme phosphoester interactions by combining mutagenesis and chemical modification of phosphate ester oxygens.
  Chem Rev, 106, 3443-3467.  
16556227 J.W.Schmidt, L.Rajeev, A.A.Salyers, and J.F.Gardner (2006).
NBU1 integrase: evidence for an altered recombination mechanism.
  Mol Microbiol, 60, 152-164.  
16885024 K.Perry, Y.Hwang, F.D.Bushman, and G.D.Van Duyne (2006).
Structural basis for specificity in the poxvirus topoisomerase.
  Mol Cell, 23, 343-354.
PDB codes: 2h7f 2h7g
16859497 L.Rajeev, A.A.Salyers, and J.F.Gardner (2006).
Characterization of the integrase of NBU1, a Bacteroides mobilizable transposon.
  Mol Microbiol, 61, 978-990.  
16990249 P.Fiorani, G.Chillemi, C.Losasso, S.Castelli, and A.Desideri (2006).
The different cleavage DNA sequence specificity explains the camptothecin resistance of the human topoisomerase I Glu418Lys mutant.
  Nucleic Acids Res, 34, 5093-5100.  
16846801 R.Balaña-Fouce, C.M.Redondo, Y.Pérez-Pertejo, R.Díaz-González, and R.M.Reguera (2006).
Targeting atypical trypanosomatid DNA topoisomerase I.
  Drug Discov Today, 11, 733-740.  
17003057 S.Bolusani, C.H.Ma, A.Paek, J.H.Konieczka, M.Jayaram, and Y.Voziyanov (2006).
Evolution of variants of yeast site-specific recombinase Flp that utilize native genomic sequences as recombination target sites.
  Nucleic Acids Res, 34, 5259-5269.  
16488610 S.Zhang, X.Li, F.Zhang, P.Yang, X.Gao, and Q.Song (2006).
Preparation of yuanhuacine and relative daphne diterpene esters from Daphne genkwa and structure-activity relationship of potent inhibitory activity against DNA topoisomerase I.
  Bioorg Med Chem, 14, 3888-3895.  
16990856 Y.Pommier (2006).
Topoisomerase I inhibitors: camptothecins and beyond.
  Nat Rev Cancer, 6, 789-802.  
16891172 Y.Pommier, J.M.Barcelo, V.A.Rao, O.Sordet, A.G.Jobson, L.Thibaut, Z.H.Miao, J.A.Seiler, H.Zhang, C.Marchand, K.Agama, J.L.Nitiss, and C.Redon (2006).
Repair of topoisomerase I-mediated DNA damage.
  Prog Nucleic Acid Res Mol Biol, 81, 179-229.  
16336270 A.Gabibov, E.Yakubovskaya, M.Lukin, P.Favorov, A.Reshetnyak, and M.Monastyrsky (2005).
Catalytic transformations of supercoiled DNA as studied by flow linear dichroism technique.
  FEBS J, 272, 6336-6343.  
15800630 D.A.Koster, V.Croquette, C.Dekker, S.Shuman, and N.H.Dekker (2005).
Friction and torque govern the relaxation of DNA supercoils by eukaryotic topoisomerase IB.
  Nature, 434, 671-674.  
16050789 D.Steverding, and K.M.Tyler (2005).
Novel antitrypanosomal agents.
  Expert Opin Investig Drugs, 14, 939-955.  
15944452 G.Chillemi, P.Fiorani, S.Castelli, A.Bruselles, P.Benedetti, and A.Desideri (2005).
Effect on DNA relaxation of the single Thr718Ala mutation in human topoisomerase I: a functional and molecular dynamics study.
  Nucleic Acids Res, 33, 3339-3350.  
16141202 H.Interthal, H.J.Chen, and J.J.Champoux (2005).
Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages.
  J Biol Chem, 280, 36518-36528.  
15920477 H.Interthal, H.J.Chen, T.E.Kehl-Fie, J.Zotzmann, J.B.Leppard, and J.J.Champoux (2005).
SCAN1 mutant Tdp1 accumulates the enzyme--DNA intermediate and causes camptothecin hypersensitivity.
  EMBO J, 24, 2224-2233.  
15830206 J.B.Leppard, and J.J.Champoux (2005).
Human DNA topoisomerase I: relaxation, roles, and damage control.
  Chromosoma, 114, 75-85.  
15793124 J.F.Marquis, I.Hardy, and M.Olivier (2005).
Topoisomerase I amino acid substitutions, Gly185Arg and Asp325Glu, confer camptothecin resistance in Leishmania donovani.
  Antimicrob Agents Chemother, 49, 1441-1446.  
16314322 L.Sari, and I.Andricioaei (2005).
Rotation of DNA around intact strand in human topoisomerase I implies distinct mechanisms for positive and negative supercoil relaxation.
  Nucleic Acids Res, 33, 6621-6634.  
15959561 M.Malanga, and F.R.Althaus (2005).
The role of poly(ADP-ribose) in the DNA damage signaling network.
  Biochem Cell Biol, 83, 354-364.  
16132345 Q.Tian, J.Zhang, T.M.Tan, E.Chan, W.Duan, S.Y.Chan, U.A.Boelsterli, P.C.Ho, H.Yang, J.S.Bian, M.Huang, Y.Z.Zhu, W.Xiong, X.Li, and S.Zhou (2005).
Human multidrug resistance associated protein 4 confers resistance to camptothecins.
  Pharm Res, 22, 1837-1853.  
16160819 T.Ishikawa, A.Tamura, H.Saito, K.Wakabayashi, and H.Nakagawa (2005).
Pharmacogenomics of the human ABC transporter ABCG2: from functional evaluation to drug molecular design.
  Naturwissenschaften, 92, 451-463.  
15948034 Z.Hu, X.Yang, P.C.Ho, E.Chan, S.Y.Chan, C.Xu, X.Li, Y.Z.Zhu, W.Duan, X.Chen, M.Huang, H.Yang, and S.Zhou (2005).
St. John's Wort modulates the toxicities and pharmacokinetics of CPT-11 (irinotecan) in rats.
  Pharm Res, 22, 902-914.  
14725760 A.C.Rodríguez, and D.Stock (2004).
Studying topoisomerases in the fourth dimension.
  Structure, 12, 7-9.  
15347588 G.Chillemi, M.Redinbo, A.Bruselles, and A.Desideri (2004).
Role of the linker domain and the 203-214 N-terminal residues in the human topoisomerase I DNA complex dynamics.
  Biophys J, 87, 4087-4097.  
15494452 J.J.Vermeersch, S.Christmann-Franck, L.V.Karabashyan, S.Fermandjian, G.Mirambeau, and P.A.Der Garabedian (2004).
Pyridoxal 5'-phosphate inactivates DNA topoisomerase IB by modifying the lysine general acid.
  Nucleic Acids Res, 32, 5649-5657.  
15139806 K.D.Corbett, and J.M.Berger (2004).
Structure, molecular mechanisms, and evolutionary relationships in DNA topoisomerases.
  Annu Rev Biophys Biomol Struct, 33, 95.  
14725763 L.Tian, C.D.Claeboe, S.M.Hecht, and S.Shuman (2004).
Remote phosphate contacts trigger assembly of the active site of DNA topoisomerase IB.
  Structure, 12, 31-40.  
  15381932 N.E.Schoemaker, I.E.Kuppens, V.Moiseyenko, B.Glimelius, M.Kjaer, H.Starkhammer, D.J.Richel, R.Smaaland, K.Bertelsen, J.P.Poulsen, E.Voznyi, J.Norum, D.Fennelly, K.M.Tveit, A.Garin, G.Gruia, A.Mourier, D.Sibaud, P.Lefebvre, J.H.Beijnen, J.H.Schellens, and W.W.ten Bokkel Huinink (2004).
A randomised phase II multicentre trial of irinotecan (CPT-11) using four different schedules in patients with metastatic colorectal cancer.
  Br J Cancer, 91, 1434-1441.  
15469908 S.Antony, P.B.Arimondo, J.S.Sun, and Y.Pommier (2004).
Position- and orientation-specific enhancement of topoisomerase I cleavage complexes by triplex DNA structures.
  Nucleic Acids Res, 32, 5163-5173.  
15472946 W.Bocian, R.Kawecki, E.Bednarek, J.Sitkowski, A.Pietrzyk, M.P.Williamson, P.E.Hansen, and L.Kozerski (2004).
Multiple binding modes of the camptothecin family to DNA oligomers.
  Chemistry, 10, 5776-5787.  
15333924 X.Qiu, and C.A.Janson (2004).
Structure of apo acyl carrier protein and a proposal to engineer protein crystallization through metal ions.
  Acta Crystallogr D Biol Crystallogr, 60, 1545-1554.
PDB code: 1t8k
12482574 C.Bailly (2003).
Homocamptothecins: potent topoisomerase I inhibitors and promising anticancer drugs.
  Crit Rev Oncol Hematol, 45, 91.  
12618186 D.R.Davies, H.Interthal, J.J.Champoux, and W.G.Hol (2003).
Crystal structure of a transition state mimic for Tdp1 assembled from vanadate, DNA, and a topoisomerase I-derived peptide.
  Chem Biol, 10, 139-147.
PDB code: 1nop
12595561 G.Chillemi, P.Fiorani, P.Benedetti, and A.Desideri (2003).
Protein concerted motions in the DNA-human topoisomerase I complex.
  Nucleic Acids Res, 31, 1525-1535.  
12711735 J.F.Carey, S.J.Schultz, L.Sisson, T.G.Fazzio, and J.J.Champoux (2003).
DNA relaxation by human topoisomerase I occurs in the closed clamp conformation of the protein.
  Proc Natl Acad Sci U S A, 100, 5640-5645.  
14585933 M.H.Woo, C.Losasso, H.Guo, L.Pattarello, P.Benedetti, and M.A.Bjornsti (2003).
Locking the DNA topoisomerase I protein clamp inhibits DNA rotation and induces cell lethality.
  Proc Natl Acad Sci U S A, 100, 13767-13772.  
14654701 M.O.Christensen, H.U.Barthelmes, F.Boege, and C.Mielke (2003).
Residues 190-210 of human topoisomerase I are required for enzyme activity in vivo but not in vitro.
  Nucleic Acids Res, 31, 7255-7263.  
12853620 P.B.Arimondo, S.Angenault, L.Halby, A.Boutorine, F.Schmidt, C.Monneret, T.Garestier, J.S.Sun, C.Bailly, and C.Hélène (2003).
Spatial organization of topoisomerase I-mediated DNA cleavage induced by camptothecin-oligonucleotide conjugates.
  Nucleic Acids Res, 31, 4031-4040.  
12941889 R.Roy, P.Trowbridge, Z.Yang, J.J.Champoux, and D.T.Simmons (2003).
The cap region of topoisomerase I binds to sites near both ends of simian virus 40 T antigen.
  J Virol, 77, 9809-9816.  
12915867 X.Chen, A.M.Oza, Z.Kusenda, Q.L.Yi, D.Kochman, M.J.Moore, A.J.Davis, and L.L.Siu (2003).
Phase I study of cisplatin, irinotecan, and epirubicin administered every 3 weeks in patients with advanced solid tumours.
  Br J Cancer, 89, 617-624.  
12598365 Y.Chen, and P.A.Rice (2003).
New insight into site-specific recombination from Flp recombinase-DNA structures.
  Annu Rev Biophys Biomol Struct, 32, 135-159.  
11809893 A.Das, C.Mandal, A.Dasgupta, T.Sengupta, and H.K.Majumder (2002).
An insight into the active site of a type I DNA topoisomerase from the kinetoplastid protozoan Leishmania donovani.
  Nucleic Acids Res, 30, 794-802.
PDB code: 1juw
12426403 B.L.Staker, K.Hjerrild, M.D.Feese, C.A.Behnke, A.B.Burgin, and L.Stewart (2002).
The mechanism of topoisomerase I poisoning by a camptothecin analog.
  Proc Natl Acad Sci U S A, 99, 15387-15392.
PDB codes: 1k4s 1k4t
12209008 D.T.Lesher, Y.Pommier, L.Stewart, and M.R.Redinbo (2002).
8-Oxoguanine rearranges the active site of human topoisomerase I.
  Proc Natl Acad Sci U S A, 99, 12102-12107.
PDB code: 1lpq
11814334 G.S.Laco, J.R.Collins, B.T.Luke, H.Kroth, J.M.Sayer, D.M.Jerina, and Y.Pommier (2002).
Human topoisomerase I inhibition: docking camptothecin and derivatives into a structure-based active site model.
  Biochemistry, 41, 1428-1435.  
12221296 J.J.Champoux (2002).
Type IA DNA topoisomerases: strictly one step at a time.
  Proc Natl Acad Sci U S A, 99, 11998-12000.  
12007989 J.J.Champoux (2002).
A first view of the structure of a type IA topoisomerase with bound DNA.
  Trends Pharmacol Sci, 23, 199-201.  
12461168 J.J.Liu, N.Sondheimer, and S.L.Lindquist (2002).
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, 99, 16446-16453.  
11914645 N.E.Schoemaker, V.M.Herben, Jong, R.C.van Waardenburg, D.Pluim, W.W.ten Bokkel Huinink, J.H.Beijnen, and J.H.Schellens (2002).
Topoisomerase I levels in white blood cells of patients with ovarian cancer treated with paclitaxel-cisplatin-topotecan in a phase I study.
  Anticancer Drugs, 13, 87-91.  
12167668 N.H.Dekker, V.V.Rybenkov, M.Duguet, N.J.Crisona, N.R.Cozzarelli, D.Bensimon, and V.Croquette (2002).
The mechanism of type IA topoisomerases.
  Proc Natl Acad Sci U S A, 99, 12126-12131.  
12069967 R.T.van Dross, and M.M.Sanders (2002).
Molecular characterization of recombinant Pneumocystis carinii topoisomerase I: differential interactions with human topoisomerase I poisons and pentamidine.
  Antimicrob Agents Chemother, 46, 2145-2154.  
12209444 V.Oleinikov, A.Sukhanova, K.Mochalov, O.Ustinova, I.Kudelina, I.Bronstein, and I.Nabiev (2002).
DNA binding induces conformational transition within human DNA topoisomerase I in solution.
  Biopolymers, 67, 369-375.  
11805286 Y.Mao, I.R.Mehl, and M.T.Muller (2002).
Subnuclear distribution of topoisomerase I is linked to ongoing transcription and p53 status.
  Proc Natl Acad Sci U S A, 99, 1235-1240.  
11446589 D.V.Bugreev, E.L.Vasyutina, V.A.Ryabinin, A.N.Sinyakov, V.N.Buneva, and G.A.Nevinsky (2001).
Inhibition of human DNA topoisomerase I by new DNA minor groove ligands: derivatives of oligo-1,3-thiazolecarboxamides.
  Antisense Nucleic Acid Drug Dev, 11, 137-147.  
11423431 G.Chillemi, T.Castrignanò, and A.Desideri (2001).
Structure and hydration of the DNA-human topoisomerase I covalent complex.
  Biophys J, 81, 490-500.  
11229469 H.A.Gussin, G.P.Ignat, J.Varga, and M.Teodorescu (2001).
Anti-topoisomerase I (anti-Scl-70) antibodies in patients with systemic lupus erythematosus.
  Arthritis Rheum, 44, 376-383.  
11395412 J.J.Champoux (2001).
DNA topoisomerases: structure, function, and mechanism.
  Annu Rev Biochem, 70, 369-413.  
11532027 J.J.Pouliot, C.A.Robertson, and H.A.Nash (2001).
Pathways for repair of topoisomerase I covalent complexes in Saccharomyces cerevisiae.
  Genes Cells, 6, 677-687.  
11470877 K.Søe, G.Dianov, H.P.Nasheuer, V.A.Bohr, F.Grosse, and T.Stevnsner (2001).
A human topoisomerase I cleavage complex is recognized by an additional human topisomerase I molecule in vitro.
  Nucleic Acids Res, 29, 3195-3203.  
11222763 L.Kozerski, A.P.Mazurek, R.Kawecki, W.Bocian, P.Krajewski, E.Bednarek, J.Sitkowski, M.P.Williamson, A.J.Moir, and P.E.Hansen (2001).
A nicked duplex decamer DNA with a PEG(6) tether.
  Nucleic Acids Res, 29, 1132-1143.
PDB code: 1g1n
11564555 S.Scaldaferro, S.Tinelli, M.E.Borgnetto, A.Azzini, and G.Capranico (2001).
Directed evolution to increase camptothecin sensitivity of human DNA topoisomerase I.
  Chem Biol, 8, 871-881.  
11264450 T.K.Li, and L.F.Liu (2001).
Tumor cell death induced by topoisomerase-targeting drugs.
  Annu Rev Pharmacol Toxicol, 41, 53-77.  
10828956 B.O.Krogh, and S.Shuman (2000).
DNA strand transfer catalyzed by vaccinia topoisomerase: peroxidolysis and hydroxylaminolysis of the covalent protein-DNA intermediate.
  Biochemistry, 39, 6422-6432.  
10911997 B.O.Krogh, and S.Shuman (2000).
Catalytic mechanism of DNA topoisomerase IB.
  Mol Cell, 5, 1035-1041.  
10756188 C.Cheng, and S.Shuman (2000).
DNA strand transfer catalyzed by vaccinia topoisomerase: ligation of DNAs containing a 3' mononucleotide overhang.
  Nucleic Acids Res, 28, 1893-1898.  
10734203 D.Sikder, and V.Nagaraja (2000).
Determination of the recognition sequence of Mycobacterium smegmatis topoisomerase I on mycobacterial genomic sequences.
  Nucleic Acids Res, 28, 1830-1837.  
10805740 D.Strumberg, A.A.Pilon, M.Smith, R.Hickey, L.Malkas, and Y.Pommier (2000).
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, 20, 3977-3987.  
11088561 H.Zhou, Y.Zhang, and Z.Ou-Yang (2000).
Elastic property of single double-stranded DNA molecules: theoretical study and comparison with experiments.
  Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics, 62, 1045-1058.  
10820030 J.T.Stivers, G.J.Jagadeesh, B.Nawrot, W.J.Stec, and S.Shuman (2000).
Stereochemical outcome and kinetic effects of Rp- and Sp-phosphorothioate substitutions at the cleavage site of vaccinia type I DNA topoisomerase.
  Biochemistry, 39, 5561-5572.  
10841763 M.R.Redinbo, J.J.Champoux, and W.G.Hol (2000).
Novel insights into catalytic mechanism from a crystal structure of human topoisomerase I in complex with DNA.
  Biochemistry, 39, 6832-6840.
PDB code: 1ej9
10677551 P.Pourquier, Y.Takebayashi, Y.Urasaki, C.Gioffre, G.Kohlhagen, and Y.Pommier (2000).
Induction of topoisomerase I cleavage complexes by 1-beta -D-arabinofuranosylcytosine (ara-C) in vitro and in ara-C-treated cells.
  Proc Natl Acad Sci U S A, 97, 1885-1890.  
10861727 Q.Li, L.A.Mitscher, and L.L.Shen (2000).
The 2-pyridone antibacterial agents: bacterial topoisomerase inhibitors.
  Med Res Rev, 20, 231-293.  
10688881 Y.Pommier, G.Kohlhagen, P.Pourquier, J.M.Sayer, H.Kroth, and D.M.Jerina (2000).
Benzo[a]pyrene diol epoxide adducts in DNA are potent suppressors of a normal topoisomerase I cleavage site and powerful inducers of other topoisomerase I cleavages.
  Proc Natl Acad Sci U S A, 97, 2040-2045.  
10995470 Y.Pommier, G.S.Laco, G.Kohlhagen, J.M.Sayer, H.Kroth, and D.M.Jerina (2000).
Position-specific trapping of topoisomerase I-DNA cleavage complexes by intercalated benzo[a]- pyrene diol epoxide adducts at the 6-amino group of adenine.
  Proc Natl Acad Sci U S A, 97, 10739-10744.  
10361305 A.J.Spiers, and D.J.Sherratt (1999).
C-terminal interactions between the XerC and XerD site-specific recombinases.
  Mol Microbiol, 32, 1031-1042.  
10574789 A.Mondragón, and R.DiGate (1999).
The structure of Escherichia coli DNA topoisomerase III.
  Structure, 7, 1373-1383.
PDB code: 1d6m
10450093 D.J.Diller, E.Pohl, M.R.Redinbo, B.T.Hovey, and W.G.Hol (1999).
A rapid method for positioning small flexible molecules, nucleic acids, and large protein fragments in experimental electron density maps.
  Proteins, 36, 512-525.  
10450094 D.J.Diller, M.R.Redinbo, E.Pohl, and W.G.Hol (1999).
A database method for automated map interpretation in protein crystallography.
  Proteins, 36, 526-541.  
10047575 D.N.Gopaul, and G.D.Duyne (1999).
Structure and mechanism in site-specific recombination.
  Curr Opin Struct Biol, 9, 14-20.  
10377382 F.Guo, D.N.Gopaul, and G.D.Van Duyne (1999).
Asymmetric DNA bending in the Cre-loxP site-specific recombination synapse.
  Proc Natl Acad Sci U S A, 96, 7143-7148.
PDB codes: 4crx 5crx
10577069 I.Grainge, and M.Jayaram (1999).
The integrase family of recombinase: organization and function of the active site.
  Mol Microbiol, 33, 449-456.  
  10224251 M.Del Poeta, D.L.Toffaletti, T.H.Rude, C.C.Dykstra, J.Heitman, and J.R.Perfect (1999).
Topoisomerase I is essential in Cryptococcus neoformans: role In pathobiology and as an antifungal target.
  Genetics, 152, 167-178.  
  10582872 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 (1999).
Comparison of in vitro activities of camptothecin and nitidine derivatives against fungal and cancer cells.
  Antimicrob Agents Chemother, 43, 2862-2868.  
  10515904 M.E.Cardenas, M.C.Cruz, M.Del Poeta, N.Chung, J.R.Perfect, and J.Heitman (1999).
Antifungal activities of antineoplastic agents: Saccharomyces cerevisiae as a model system to study drug action.
  Clin Microbiol Rev, 12, 583-611.  
10047584 M.R.Redinbo, J.J.Champoux, and W.G.Hol (1999).
Structural insights into the function of type IB topoisomerases.
  Curr Opin Struct Biol, 9, 29-36.  
10500195 R.J.Reid, P.Fiorani, M.Sugawara, and M.A.Bjornsti (1999).
CDC45 and DPB11 are required for processive DNA replication and resistance to DNA topoisomerase I-mediated DNA damage.
  Proc Natl Acad Sci U S A, 96, 11440-11445.  
10024172 W.Wang, K.Riedel, P.Lynch, C.Y.Chien, G.T.Montelione, and R.M.Krug (1999).
RNA binding by the novel helical domain of the influenza virus NS1 protein requires its dimer structure and a small number of specific basic amino acids.
  RNA, 5, 195-205.  
10194356 X.Wang, X.Zhou, and S.M.Hecht (1999).
Role of the 20-hydroxyl group in camptothecin binding by the topoisomerase I-DNA binary complex.
  Biochemistry, 38, 4374-4381.  
11504505 Y.Pommier, P.Pourquier, Y.Urasaki, J.Wu, and G.S.Laco (1999).
Topoisomerase I inhibitors: selectivity and cellular resistance.
  Drug Resist Updat, 2, 307-318.  
9634692 D.B.Wigley (1998).
Teaching a new dog old tricks?
  Structure, 6, 543-548.  
9568707 D.J.Sherratt, and D.B.Wigley (1998).
Conserved themes but novel activities in recombinases and topoisomerases.
  Cell, 93, 149-152.  
9670032 D.N.Gopaul, F.Guo, and G.D.Van Duyne (1998).
Structure of the Holliday junction intermediate in Cre-loxP site-specific recombination.
  EMBO J, 17, 4175-4187.
PDB codes: 2crx 3crx
9772192 F.Fleury, A.Ianoul, E.Kryukov, A.Sukhanova, I.Kudelina, A.Wynne-Jones, I.B.Bronstein, M.Maizieres, M.Berjot, G.G.Dodson, A.J.Wilkinson, J.A.Holden, A.V.Feofanov, A.J.Alix, J.C.Jardillier, and I.Nabiev (1998).
Raman and CD spectroscopy of recombinant 68-kDa DNA human topoisomerase I and its complex with suicide DNA-substrate.
  Biochemistry, 37, 14630-14642.  
9748476 J.M.Berger (1998).
Structure of DNA topoisomerases.
  Biochim Biophys Acta, 1400, 3.  
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