Degradation of DNA and structure-activity relationship between bleomycins A sub 2 and B sub 2 in the absence of DNA repair

Journal Article · Tue Feb 06 04:00:00 EST 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00457a033· OSTI ID:6709383

Moore, C W ^[1]

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1. City Univ. of New York, NY (USA)

The contribution of DNA repair to the net number of DNA breaks produced during chemical degradation of DNA was determined by using temperature-sensitive mutant cells deficient in ATP-dependent DNA ligase. In a very sensitive assay for determining lesions introduced into Saccharomyces cerevisiae DNAs, 2-{sup 14}C- and 6-{sup 3}H-prelabeled DNAs from ligase-proficient and ligase-deficient cells were sedimented together through precalibrated, isokinetic alkaline sucrose gradients. DNA ligation was slower after chemical degradation of DNA by bleomycin than after {gamma} irradiation. DNA breaks increased approximately linearly with drug concentrations, and were approximately equivalent for ligase-proficient and ligase-deficient cells. These results were unexpected because ligase-deficient, but not ligase-proficient, cells lacked the capacity to eliminate DNA breaks produced by bleomycin. The results indicated that DNA repair did not occur during the chemical degradation of DNA under the experimental conditions. Bleomycin B{sub 2} produced considerably more DNA breaks than bleomycin A{sub 2} over a range of concentrations in ligase-proficient cells, which tolerated higher numbers of DNA breaks in general than ligase-deficient cells. The chemical analogues are structurally identical except for their cationic C-terminal amine. The actual number of DNA breaks produced by bleomycin A{sub 2} or bleomycin B{sub 2}, and not the concentration of bleomycin A{sub 2} or bleomycin B{sub 2} per se, determined the amount of cell killing. DNA repair is critical in quantitating DNA breaks produced by chemicals, but was ruled out as a factor in the higher DNA breakage by bleomycin B{sub 2} than bleomycin A{sub 2}.

• OSTI ID: 6709383
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 29:5; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
BIODEGRADATION
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BLEOMYCIN
CELL KILLING
CHEMICAL REACTIONS
DECOMPOSITION
DNA
DNA REPAIR
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTROMAGNETIC RADIATION
ENZYMES
EUMYCOTA
FUNGI
GAMMA RADIATION
GENETIC MAPPING
IONIZING RADIATIONS
LIGASES
MAPPING
MICROORGANISMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PLANTS
PURIFICATION
RADIATIONS
RADIOINDUCTION
RECOVERY
REPAIR
SACCHAROMYCES
SACCHAROMYCES CEREVISIAE
STRAND BREAKS
STRUCTURE-ACTIVITY RELATIONSHIPS
YEASTS