Molecular mechanisms of DNA repair inhibition by caffeine

Journal Article · Tue May 01 04:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.9.3522· OSTI ID:7043265

Selby, C P; Sancar, A ^[1]

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1. Univ. of North Carolina School of Medicine, Chapel Hill (USA)

Caffeine potentiates the mutagenic and lethal effects of genotoxic agents. It is thought that this is due, at least in some organisms, to inhibition of DNA repair. However, direct evidence for inhibition of repair enzymes has been lacking. Using purified Escherichia coli DNA photolyase and (A)BC excinuclease, we show that the drug inhibits photoreactivation and nucleotide excision repair by two different mechanisms. Caffeine inhibits photoreactivation by interfering with the specific binding of photolyase to damaged DNA, and it inhibits nucleotide excision repair by promoting nonspecific binding of the damage-recognition subunit, UvrA, of (A)BC excinuclease. A number of other intercalators, including acriflavin and ethidium bromide, appear to inhibit the excinuclease by a similar mechanism--that is, by trapping the UvrA subunit in nonproductive complexes on undamaged DNA.

• OSTI ID: 7043265
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:9; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

560130* -- Radiation Effects on Microorganisms
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANALEPTICS
AROMATICS
AZAARENES
BACTERIA
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CAFFEINE
CENTRAL NERVOUS SYSTEM AGENTS
DNA REPAIR
DRUGS
ELECTROMAGNETIC RADIATION
ENZYMES
ESCHERICHIA COLI
ESTERASES
EXCISION REPAIR
GENETIC EFFECTS
GENETIC RADIATION EFFECTS
HETEROCYCLIC COMPOUNDS
HYDROLASES
INHIBITION
MICROORGANISMS
NUCLEASES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PHOSPHODIESTERASES
PURINES
RADIATION EFFECTS
RADIATIONS
RADIOSENSITIVITY EFFECTS
RECOVERY
REPAIR
ULTRAVIOLET RADIATION
XANTHINES