Affiliation:
1. Department of Radiology and Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520
Abstract
We have investigated some biological consequences of light-induced psoralen-deoxyribonucleic acid (DNA) adducts and find that for several
Escherichia coli
functions (killing of strain AB2480
recA13 uvrA6
, inactivation of phage lambda plaque-forming ability in wild type and
uvrA6
hosts, loss of ability to transmit intact F
lac
+
episomes), a light exposure sufficient for production of a single cross-link per DNA molecule correlates well with the biological consequence. Although one cross-link per genome is apparently lethal to
recA13 uvr
−
strains, mutants carrying the
recA13
or
uvrA6
markers survive light exposures producing 6.7 and 16 cross-links per genome, respectively, and wild-type cells recover from 65 psoralen cross-links. Evidently, the excision and recombinational repair systems complement one another in reconstructing an intact genome from cellular DNA containing psoralen photoproducts. The above bacterial and phage strains, in which DNA repair processes are minimized, are also extremely sensitive to pyrimidine dimer-forming 254-nm UV light (without psoralen), and were expected to respond similarly to formation of psoralen-pyrimidine base monoadducts in their DNA. Since the biological inactivation by psoralen correlates well with cross-link formation, we suggest that the sensitizing action of this drug primarily derives from its ability to form DNA cross-links.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
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