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Papers In Press, published online ahead of print October 24, 2001
Nutritional Science, Kobe-Gakuin University, Kobe, Hyogo 651-2180
Corresponding Author: mizushin{at}nutr.kobegakuin.ac.jp
Solanapyrone A, a phytotoxin and enzyme inhibitor isolated from a fungus (SUT 01B1-2), selectively inhibits the activities of mammalian DNA polymerase beta and lambda (pol beta and lambda) in vitro. The IC50 values of the compound were 30 micro M for pol beta and 37 micro M for pol lambda. Since pol beta and lambda are in a family and their three-dimensional structures are thought to be highly similar to each other, we used pol beta to analyze the biochemical relationship with solanapyrone A. On pol beta, solanapyrone A antagonistically competed with both the DNA template and the nucleotide substrate. BIAcore analysis demonstrated that solanapyrone A bound selectively to the N-terminal 8 kDa domain of pol beta. This domain is known to bind single-stranded DNA (ssDNA), provide 5'-phosphate recognition of gapped DNA, and cleave the sugar-phosphate bond 3' to an intact apurinic/apyrimidinic (AP) site (i.e. AP lyase activity), including 5'-deoxyribose phosphate lyase activity. Solanapyrone A inhibited the ssDNA binding activity, but did not influence the activities of the 5'-phosphate recognition in gapped DNA structures, and the AP lyase. Based on these results, the inhibitory mechanism of solanapyrone A is discussed.
J. Biol. Chem, 10.1074/jbc.M105144200
Submitted on June 5, 2001
Revised on October 4, 2001
Accepted on October 24, 2001
A plant phytotoxin, solanapyrone A, is an inhibitor of DNA polymerase beta and lambda
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