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Mimosine has been reported to specifically prevent initiation of
DNA replication in the chromosomes of mammalian nuclei. To test this
hypothesis, the effects of mimosine were examined in several DNA
replication systems and compared with the effects of aphidicolin, a
specific inhibitor of replicative DNA polymerases. Our results
demonstrated that mimosine inhibits DNA synthesis in mitochondrial,
nuclear, and simian virus 40 (SV40) genomes to a similar extent.
Furthermore, mimosine and aphidicolin were indistinguishable in their
ability to arrest SV40 replication forks and mammalian nuclear
chromosomal replication forks. In contrast to aphidicolin, mimosine did
not inhibit DNA replication in lysates of mammalian cells supplied with
exogenous deoxyribonucleotide triphosphate precursors for DNA
synthesis. Mimosine also had no effect on initiation or elongation of
DNA replication in Xenopus eggs or egg extracts containing
high levels of deoxyribonucleotide triphosphates. In parallel with its
inhibitory effect on DNA synthesis in mammalian cells, mimosine altered
deoxyribonucleotide triphosphate pools in a manner similar to that
reported for another DNA replication inhibitor that affects
deoxyribonucleotide metabolism, hydroxyurea. Taken together, these
results show that mimosine inhibits DNA synthesis at the level of
elongation of nascent chains by altering deoxyribonucleotide
metabolism.
Volume 270,
Number 16,
Issue of April 21, pp. 9597-9606, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
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