TY - JOUR
T1 - Kohamaic acid A, a novel sesterterpenic acid, inhibits activities of DNA polymerases from deuterostomes
AU - Mizushina, Yoshiyuki
AU - Murakami, Chikako
AU - Yogi, Kentaro
AU - Ueda, Katsuhiro
AU - Ishidoh, Tomomi
AU - Takemura, Masaharu
AU - Perpelescu, Marinela
AU - Suzuki, Motoshi
AU - Oshige, Masahiko
AU - Yamaguchi, Toyofumi
AU - Saneyoshi, Mineo
AU - Yoshida, Hiromi
AU - Sakaguchi, Kengo
N1 - Funding Information:
We deeply thank Dr. S. Yoshida of Nagoya University for his valuable discussions about the inhibitor. We are grateful to Dr. S. Linn and Dr. H. Asahara of University of California, Berkeley for preparing human DNA polymerase ε. This work was partly supported by the Sasakawa Scientific Research Grant (to C.M.) from The Japan Science Society, by Grant-in-Aid for Kobe-Gakuin University Joint Research (B) (to Y.M., C.M. and H.Y.) and by Grant-in-Aid 14780466 for Scientific Research (to Y.M.) from the Ministry of Education, Science, Sports and Culture, Japan.
PY - 2003/5/30
Y1 - 2003/5/30
N2 - 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. α, β, γ, δ and ε) 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. IC50 values for DNA polymerases of mammals and fish occurred at approximately 5.8-14.9 μM and those of sea urchin at 6.1-30.3 μM. In the sea urchin DNA polymerases, the activities of the replicative DNA polymerases such as α, δ and ε were more strongly inhibited than that of the repair-related pol. β. 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.
AB - 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. α, β, γ, δ and ε) 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. IC50 values for DNA polymerases of mammals and fish occurred at approximately 5.8-14.9 μM and those of sea urchin at 6.1-30.3 μM. In the sea urchin DNA polymerases, the activities of the replicative DNA polymerases such as α, δ and ε were more strongly inhibited than that of the repair-related pol. β. 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.
UR - https://www.scopus.com/pages/publications/0037968241
UR - https://www.scopus.com/pages/publications/0037968241#tab=citedBy
U2 - 10.1016/S1570-9639(03)00108-0
DO - 10.1016/S1570-9639(03)00108-0
M3 - Article
C2 - 12758147
AN - SCOPUS:0037968241
SN - 1570-9639
VL - 1648
SP - 55
EP - 61
JO - Biochimica et Biophysica Acta - Proteins and Proteomics
JF - Biochimica et Biophysica Acta - Proteins and Proteomics
IS - 1-2
ER -