Home LiteratureArticle Details
PMID: 7991579 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Disruption of a topoisomerase-DNA cleavage complex by a DNA helicase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 25 ·1994-12-06 ·Pages 12031-5

Howard MT, Neece SH, Matson SW, Kreuzer KN

Abstract

The type II DNA topoisomerases are targets for a variety of chemotherapeutic agents, including the antibacterial quinolones and several families of antitumor drugs. These agents stabilize an enzyme-DNA cleavage complex that consists of the topoisomerase covalently linked to the 5' phosphates of a double-stranded DNA break. Although the drug-stabilized cleavage complex is readily reversible, it can result in cell death by a mechanism that remains uncertain. Here we demonstrate that the action of a DNA helicase can convert the cleavage complex into a nonreversible DNA break by displacing DNA strands from the complex. Formation of a nonreversible DNA break, induced by a DNA helicase, could explain the cytotoxicity of these topoisomerase poisons.

MeSH Terms
Adenosine Triphosphatases/metabolism Amsacrine Bacteriophage T4/enzymology Base Sequence DNA Helicases DNA Topoisomerases, Type II/isolation & purification,metabolism Electrophoresis, Polyacrylamide Gel Escherichia coli/enzymology Models, Structural Molecular Sequence Data Plasmids/isolation & purification,metabolism Protein Binding Substrate Specificity
Chemicals
Amsacrine Adenosine Triphosphatases DNA Helicases DNA Topoisomerases, Type II
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Howard M T
Department of Biology, University of North Carolina, Chapel Hill 27599.
Neece S H
Matson S W
Kreuzer K N
References (39)
39 references, click to expand
  1. Nalidixic acid resistance: a second genetic character involved in DNA gyrase activity.
    Proc Natl Acad Sci U S A. 1977 Nov;74(11):4772-6 PMID: 337300
  2. Mechanism of action of nalidixic acid: purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme.
    Proc Natl Acad Sci U S A. 1977 Nov;74(11):4767-71 PMID: 200930
  3. Double strand DNA cleavage by type II DNA topoisomerase from Drosophila melanogaster.
    J Biol Chem. 1983 Jul 10;258(13):8421-8 PMID: 6305984
  4. Escherichia coli phage T4 topoisomerase.
    Methods Enzymol. 1983;100:144-60 PMID: 6312256
  5. Mechanism of antitumor drug action: poisoning of mammalian DNA topoisomerase II on DNA by 4'-(9-acridinylamino)-methanesulfon-m-anisidide.
    Proc Natl Acad Sci U S A. 1984 Mar;81(5):1361-5 PMID: 6324188
  6. Site-specific recognition of bacteriophage T4 DNA by T4 type II DNA topoisomerase and Escherichia coli DNA gyrase.
    J Biol Chem. 1984 Apr 25;259(8):5339-46 PMID: 6325431
  7. Recognition of single-stranded DNA by the bacteriophage T4-induced type II topoisomerase.
    J Biol Chem. 1984 Apr 25;259(8):5347-54 PMID: 6325432
  8. Identification of the breakage-reunion subunit of T4 DNA topoisomerase.
    J Biol Chem. 1984 Jul 25;259(14):9177-81 PMID: 6086624
  9. DNA topoisomerases.
    Annu Rev Biochem. 1985;54:665-97 PMID: 2992360
  10. Mechanistic aspects of DNA topoisomerases.
    Adv Protein Chem. 1986;38:69-107 PMID: 3026152
  11. DNA helicase II of Escherichia coli. Characterization of the single-stranded DNA-dependent NTPase and helicase activities.
    J Biol Chem. 1987 Feb 15;262(5):2066-76 PMID: 3029063
  12. Calcium-promoted DNA cleavage by eukaryotic topoisomerase II: trapping the covalent enzyme-DNA complex in an active form.
    Biochemistry. 1987 Jul 14;26(14):4303-9 PMID: 2822084
  13. Hotspot sites for acridine-induced frameshift mutations in bacteriophage T4 correspond to sites of action of the T4 type II topoisomerase.
    J Mol Biol. 1988 Apr 20;200(4):665-80 PMID: 2842508
  14. DNA topoisomerase-targeting antitumor drugs can be studied in yeast.
    Proc Natl Acad Sci U S A. 1988 Oct;85(20):7501-5 PMID: 2845409
  15. Evidence that DNA topoisomerase I is necessary for the cytotoxic effects of camptothecin.
    Mol Pharmacol. 1988 Dec;34(6):755-60 PMID: 2849043
  16. Bacteriophage T4 DNA topoisomerase is the target of antitumor agent 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) in T4-infected Escherichia coli.
    Proc Natl Acad Sci U S A. 1989 Feb;86(4):1307-11 PMID: 2537494
  17. Arrest of replication forks by drug-stabilized topoisomerase I-DNA cleavable complexes as a mechanism of cell killing by camptothecin.
    Cancer Res. 1989 Sep 15;49(18):5077-82 PMID: 2548710
  18. DNA topoisomerase poisons as antitumor drugs.
    Annu Rev Biochem. 1989;58:351-75 PMID: 2549853
  19. Escherichia coli helicase II (uvrD) protein can completely unwind fully duplex linear and nicked circular DNA.
    J Biol Chem. 1989 Oct 15;264(29):17502-12 PMID: 2529260
  20. Differential requirement of DNA replication for the cytotoxicity of DNA topoisomerase I and II inhibitors in Chinese hamster DC3F cells.
    Cancer Res. 1989 Nov 15;49(22):6365-8 PMID: 2553254
  21. Topoisomerase-targeting antitumor drugs.
    Biochim Biophys Acta. 1989 Dec 17;989(2):163-77 PMID: 2557085
  22. Mutational alteration of the breakage/resealing subunit of bacteriophage T4 DNA topoisomerase confers resistance to antitumor agent m-AMSA.
    Mol Gen Genet. 1990 Mar;221(1):27-32 PMID: 2157956
  23. DNA helicases.
    Annu Rev Biochem. 1990;59:289-329 PMID: 2165383
  24. DNA double-strand break repair pathways and cellular tolerance to inhibitors of topoisomerase II.
    Cancer Res. 1990 Sep 15;50(18):5778-83 PMID: 2168280
  25. Involvement of nucleic acid synthesis in cell killing mechanisms of topoisomerase poisons.
    Cancer Res. 1990 Nov 1;50(21):6919-24 PMID: 1698546
  26. Studies of the topoisomerase II-mediated cleavage and religation reactions by use of a suicidal double-stranded DNA substrate.
    J Biol Chem. 1991 May 15;266(14):9203-10 PMID: 1851170
  27. The role of topoisomerase II in drug resistance.
    Life Sci. 1991;48(23):2195-205 PMID: 1646358
  28. Inhibition of DNA helicase II unwinding and ATPase activities by DNA-interacting ligands. Kinetics and specificity.
    J Biol Chem. 1992 May 25;267(15):10683-9 PMID: 1534088
  29. Helicase inhibition by anthracycline anticancer agents.
    Mol Pharmacol. 1992 Jun;41(6):993-8 PMID: 1614415
  30. 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 Res. 1993 Jan 1;53(1):89-93 PMID: 8380128
  31. Overexpression, purification, DNA binding, and dimerization of the Escherichia coli uvrD gene product (helicase II).
    Biochemistry. 1993 Jan 19;32(2):602-12 PMID: 8380701
  32. The DNA helicase activities of Rad3 protein of Saccharomyces cerevisiae and helicase II of Escherichia coli are differentially inhibited by covalent and noncovalent DNA modifications.
    J Biol Chem. 1993 May 15;268(14):10386-92 PMID: 8387518
  33. Mutational analysis of a type II topoisomerase cleavage site: distinct requirements for enzyme and inhibitors.
    EMBO J. 1993 May;12(5):2085-97 PMID: 8387918
  34. Antihelicase action of DNA-binding anticancer agents: relationship to guanosine-cytidine intercalator binding.
    Mol Pharmacol. 1993 Nov;44(5):1064-9 PMID: 8246909
  35. Interaction between replication forks and topoisomerase I-DNA cleavable complexes: studies in a cell-free SV40 DNA replication system.
    Cancer Res. 1993 Dec 15;53(24):5908-14 PMID: 8261402
  36. A dominant negative allele of the Escherichia coli uvrD gene encoding DNA helicase II. A biochemical and genetic characterization.
    J Mol Biol. 1994 Jan 14;235(2):424-35 PMID: 8289272
  37. DNA helicases: enzymes with essential roles in all aspects of DNA metabolism.
    Bioessays. 1994 Jan;16(1):13-22 PMID: 8141804
  38. DNA topoisomerases: essential enzymes and lethal targets.
    Annu Rev Pharmacol Toxicol. 1994;34:191-218 PMID: 8042851
  39. Escherichia coli mutants thermosensitive for deoxyribonucleic acid gyrase subunit A: effects on deoxyribonucleic acid replication, transcription, and bacteriophage growth.
    J Bacteriol. 1979 Nov;140(2):424-35 PMID: 227840
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.25.12031
Published
1994-12-06
Pages
12031-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC45370
Subset
IM
Grants
NCI NIH HHS · CA60836 · United States
NIGMS NIH HHS · GM33476 · United States
External Links
PubMed source DOI: 10.1073/pnas.91.25.12031 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2