Petasiphenol, a bio-antimutagen isolated from a Japanese vegetable,
Petasites japonicus,selectively inhibits the activities of mammalian DNA polymerase
(pol
) in vitro. The compound didnot influence the activities of replicative DNA polymerases such as
,
,
and but also showed no effecteven on the pol
activity, the three-dimensional structure of which is thought to be highly similar to pol
. The inhibitory effect of petasiphenol on intact pol
including the BRCA1 C-terminus (BRCT) domainwas dose-dependent,
and 50% inhibition was observed at a concentration of 7.8
M. The petasiphenol-induced inhibition of the pol
activity was noncompetitive with respect to both the DNA template-primer
and the dNTP substrate. Petasiphenol did not only inhibit the activity of the truncated pol
includingthe pol
-like core, in which the BRCT motif was deleted in its N-terminal region. BIAcore analysisdemonstrated that petasiphenol bound selectively to the N-terminal domain of pol
but did not bind tothe C-terminal region. On the basis of these results, the pol
inhibitory mechanism of petasiphenol isdiscussed.