Abstract
1-β-D-ARABINOFURANOSYL CYTOSINE (ara-C) and 9-β-D-arabinofuranosyl adenine (ara-A) are potent antileukaemic and antiviral agents which inhibit DNA replication in various organisms1–3. Two plausible hypotheses for their cytotoxic action centre on the replicative DNA polymerase: in model 1 the triphosphate derivative of ara-C or ara-A inhibits competitively the utilisation of the corresponding deoxyribonucleoside triphosphate in the DNA polymerase reaction, and in model 2 the analogue is incorporated into DNA and this lesion impedes synthesis by, for example, providing a poor primer for further chain elongation. Although both of these effects have been demonstrated in vitro, the target in vivo for the analogues has not been firmly established, in part because metabolites of these drugs inhibit a number of purified nucleic acid enzymes1–4. Bacterial mutants with altered drug sensitivity could be decisive in determining the mechanism of inhibition and are the subject of this report.
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RASHBAUM, S., COZZARELLI, N. Mechanism of DNA synthesis inhibition by arabinosyl cytosine and arabinosyl adenine. Nature 264, 679–680 (1976). https://doi.org/10.1038/264679a0
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DOI: https://doi.org/10.1038/264679a0
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