Camptothecin, a specific inhibitor of type I DNA topoisomerase, induces DNA breakage at replication forks

Journal Article · Mon Aug 01 04:00:00 EDT 1988 · Mol. Cell. Biol.; (United States)

DOI:https://doi.org/10.1128/MCB.8.8.3026· OSTI ID:6864765

Avemann, K; Knippers, R; Koller, T; Sogo, J M

The structure of replicating simian virus 40 minichromosomes, extracted from camptothecin-treated infected cells, was investigated by biochemical and electron microscopic methods. The authors found that camptothecin frequently induced breaks at replication forks close to the replicative growth points. Replication branches were disrupted at about equal frequencies at the leading and the lagging strand sides of the fork. Since camptothecin is known to be a specific inhibitor of type I DNA topoisomerase, the authors suggest that this enzyme is acting very near the replication forks. This conclusion was supported by experiments with aphidicolin, a drug that blocks replicative fork movement, but did not prevent the camptothecin-induced breakage of replication forks. The drug teniposide, and inhibitor of type II DNA topoisomerase, had only minor effects on the structure of these replicative intermediates.

• Research Organization: Fakultat fur Biologie, Universitat Konstanz, D-7750 Konstanz (DE)
• OSTI ID: 6864765
• Journal Information: Mol. Cell. Biol.; (United States), Journal Name: Mol. Cell. Biol.; (United States) Vol. 8:8; ISSN MCEBD
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
BIOLOGICAL FUNCTIONS
BIOLOGICAL PATHWAYS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
DNA HELICASES
DNA REPAIR
DNA REPLICATION
DRUGS
ELECTRON MICROSCOPY
ENZYME INHIBITORS
ENZYMES
FUNCTIONS
GENE RECOMBINATION PROTEINS
ISOMERASES
MICROORGANISMS
MICROSCOPY
NUCLEIC ACID REPLICATION
NUCLEOPROTEINS
ORGANIC COMPOUNDS
PARASITES
PROTEINS
RECOVERY
REPAIR
SIMIAN VIRUS
STRAND BREAKS
VIRUSES