Kohamaic acid A, a novel sesterterpenic acid, inhibits activities of DNA polymerases from deuterostomes.
We previously found and isolated a novel natural product, designated kohamaic acid A (KA-A), which inhibited the first cleavage of fertilized sea urchin eggs. In this paper, we report that this compound could selectively inhibit the activities of DNA polymerases (pol. alpha, beta, gamma, delta and epsilon ) only from species in the deuterostome branch in the animal kingdom, like sea urchin, fish and mammals, but not from protostomes including insects (fruit fly, Drosophila melanogaster) and mollusks (octopus and oyster). Inhibition of deuterostome DNA polymerases was dose dependent. IC(50) values for DNA polymerases of mammals and fish occurred at approximately 5.8-14.9 microM and those of sea urchin at 6.1-30.3 microM. In the sea urchin DNA polymerases, the activities of the replicative DNA polymerases such as alpha, delta and epsilon were more strongly inhibited than that of the repair-related pol. beta. KA-A is an inhibitor of replicative DNA polymerases from the deuterostome species, and subsequently, the inhibition of the first cleavage of fertilized sea urchin eggs might occur as a result of the suppression of DNA replication.
Mizushina
Yoshiyuki
Y
Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi, Hyogo 651-2180, Japan. mizushin@nutr.kobegakuin.ac.jp
Murakami
Chikako
C
Yogi
Kentaro
K
Ueda
Katsuhiro
K
Ishidoh
Tomomi
T
Takemura
Masaharu
M
Perpelescu
Marinela
M
Suzuki
Motoshi
M
Oshige
Masahiko
M
Yamaguchi
Toyofumi
T
Saneyoshi
Mineo
M
Yoshida
Hiromi
H
Sakaguchi
Kengo
K
D000818:Animals; D002970:Cleavage Stage, Ovum / Q000201:enzymology; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D019384:Nucleic Acid Synthesis Inhibitors; D012617:Sea Urchins / Q000201:enzymology; D054830:Sesterterpenes; D013045:Species Specificity; D013729:Terpenes / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D019384:Nucleic Acid Synthesis Inhibitors; D054830:Sesterterpenes; D013729:Terpenes; C475030:kohamaic acid A; D004259:DNA-Directed DNA Polymerase