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Termination of Deoxyribonucleic Acid in Escherichia coli by 2',3'-Dideoxyadenosine¹

^a Department of Therapeutic Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

ABSTRACT

2',3'-Dideoxyadenosine was previously shown to be lethal to Escherichia coli and to inhibit deoxyribonucleic acid (DNA) synthesis irreversibly in this organism. It was also shown that triphosphate of this analogue terminates DNA chains in an in vitro system. Data presented here show that the nucleoside is relatively insensitive to E. coli adenosine deaminase and is converted intracellularly into the dideoxynucleotide, including the triphosphate. Thymine nucleotide pools were not reduced in inhibited bacteria, nor did preformed DNA break down. Some adenine was liberated from the dideoxyadenosine on incubation, and the latter was incorporated into ribonucleic acid. Nevertheless, about 4,000 molecules of the dideoxynucleoside were incorporated into DNA per cell. The dideoxynucleotide occurred in DNA chains in a terminal position, liberated selectively by venom phosphodiesterase. The possible nature of the lethal event is discussed.

² Trainee under Public Health Service predoctoral training grant T01-AI-00357 from the National Institute of Allergy and Infectious Diseases.

¹ Taken from a dissertation presented by Lorraine Toji to the faculty of the Graduate School of Arts and Sciences of the University of Pennsylvania in partial fulfillment of the requirements for the Ph.D. degree.

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