Specificity and completeness of inhibition of DNA repair by novobiocin and aphidicolin

Journal Article · Fri Jan 01 04:00:00 EST 1982 · Carcinogenesis (N.Y.); (United States)

DOI:https://doi.org/10.1093/carcin/3.10.1171· OSTI ID:6252050

Cleaver, J E

Novobiocin and aphidicolin were both potent inhibitors of excision repair of u.v.-induced damage to DNA in human embryonic fibroblasts, and both also inhibited semiconservative DNA replication even more strongly. The mechanism of action of these two drugs is, however, different. Novobiocin inhibited repair replication without accumulating single-strand breaks, but aphidicolin inhibited repair replication with the accumulation of numerous single-strand breaks. Novobiocin appears to inhibit repair at an earlier stage than aphidicolin, which may indicate that DNA topoisomerases play a role in eukaryotic DNA repair. Digestion of DNA by exonuclease III indicated that repair patches in novobiocin-treated cells contained no excess 3'OH termini, whereas up to 40% of the repaired DNA in aphidicolin-treated cells had free 3'OH termini. Therefore, although aphidicolin resulted in the accumulation of single-strand breaks, many of the repair events escaped inhibition and the number of breaks is an underestimate of the true number of repair events.

• Research Organization: Laboratory of Radiobiology and Environmental Health, University of California, San Francisco
• OSTI ID: 6252050
• Journal Information: Carcinogenesis (N.Y.); (United States), Journal Name: Carcinogenesis (N.Y.); (United States) Vol. 3:10; ISSN CRNGD
• Country of Publication: United States
• Language: English

Related Subjects

560111* -- Radiation Effects on Biochemicals-- In Vitro-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANTI-INFECTIVE AGENTS
ANTIMICROBIAL AGENTS
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CONNECTIVE TISSUE CELLS
DNA
DNA REPLICATION
DRUGS
ELECTROMAGNETIC RADIATION
FIBROBLASTS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
ORGANIC COMPOUNDS
RADIATIONS
RADIOSENSITIVITY EFFECTS
RECOVERY
REPAIR
SOMATIC CELLS
STRAND BREAKS
ULTRAVIOLET RADIATION