title: Kohamaic acid A, a novel sesterterpenic acid, inhibits activities of DNA polymerases from deuterostomes.
abstract: 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.
authors.affiliation: Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi, Hyogo 651-2180, Japan. mizushin@nutr.kobegakuin.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mizushina
authors.forename: Chikako
authors.initials: C
authors.lastname: Murakami
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yogi
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Ueda
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ishidoh
authors.forename: Masaharu
authors.initials: M
authors.lastname: Takemura
authors.forename: Marinela
authors.initials: M
authors.lastname: Perpelescu
authors.forename: Motoshi
authors.initials: M
authors.lastname: Suzuki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Oshige
authors.forename: Toyofumi
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Mineo
authors.initials: M
authors.lastname: Saneyoshi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Kengo
authors.initials: K
authors.lastname: Sakaguchi
mesh_terms: 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
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D054830:Sesterterpenes; D013729:Terpenes; C475030:kohamaic acid A; D004259:DNA-Directed DNA Polymerase