Inhibition of pea chloroplast DNA helicase unwinding and ATPase activities by DNA-interacting ligands.

Inhibition of pea chloroplast DNA helicase unwinding and ATPase activities by DNA-interacting ligands.
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DNA 相互作用配体抑制豌豆叶绿体 DNA 解旋酶解旋和 ATP 酶活性。

DOI:
10.1006/bbrc.1998.8363
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发表时间:
1998
影响因子:
3.1
通讯作者:
T. Phan
T. Phan
中科院分区:
生物学4区
文献类型:
--
作者:
N. Tuteja;T. Phan

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DNA 解旋酶以 ATP 依赖性方式解旋双链 DNA,因此在 DNA 复制、修复、重组和转录中发挥重要作用。任何能够调节 DNA 解旋酶活性的 DNA 相互作用配体都可能中断几乎所有类型的 DNA 处理。目前还没有关于各种细胞毒性 DNA 相互作用配体对细胞器解旋酶的影响的研究。我们确定了喜树碱、VP-16(依托泊苷)、玫瑰树碱、金雀异黄素、新生霉素、m-AMSA、放线菌素 C1、溴化乙锭、柔红霉素和诺加霉素对来自豌豆 (Pisum sativum) 的纯化叶绿体 DNA 解旋酶的解旋和 ATP 酶活性的影响。我们的研究表明,DNA 嵌入配体放线菌素 C1、溴化乙锭、柔红霉素和诺加霉素抑制 DNA 解旋活性,表观 Ki 分别为 2.9 microM、3.0 microM、1.4 microM 和 1.0 microM。这四种抑制剂还抑制豌豆叶绿体DNA解旋酶的ATP酶活性。这些结果表明,抑制剂插入 DNA 中会产生复合物,阻碍叶绿体 DNA 解旋酶的易位,从而抑制解旋活性和 ATP 水解。这项研究将有助于了解细胞器 DNA 解旋酶解旋机制以及这些 DNA 相互作用配体抑制细胞功能的机制。
DNA helicases unwind the duplex DNA in an ATP dependent manner and thus play an essential role in DNA replication, repair, recombination and transcription. Any DNA-interacting ligand which will modulate DNA helicase activity may interrupt practically all kinds of DNA transactions. There are no studies on the effect of various cytotoxic DNA-interacting ligands on organelle helicases. We have determined the effect of camptothecin, VP-16 (etoposide), ellipticine, genistein, novobiocin, m-AMSA, actinomycin C1, ethidium bromide, daunorubicin and nogalamycin on unwinding and ATPase activities of purified chloroplast DNA helicase from pea (Pisum sativum). Our study has shown that DNA-intercalating ligands actinomycin C1, ethidium bromide, daunorubicin and nogalamycin were inhibiting the DNA unwinding activity with an apparent Ki of 2.9 microM, 3.0 microM, 1.4 microM and 1.0 microM, respectively. These four inhibitors also inhibited the ATPase activity of pea chloroplast DNA helicase. These results indicate that the intercalation of the inhibitors into DNA generates a complex that impedes the translocation of chloroplast DNA helicase, resulting in both inhibition of unwinding activity and ATP hydrolysis. This study would be useful for understanding the mechanism of organelle DNA helicase unwinding and the mechanism by which these DNA-interacting ligands inhibit cellular function.
DOI: 10.1016/s0021-9258(19)50072-2
发表时间: 1992-05
期刊: The Journal of biological chemistry
影响因子: --
作者:
J. W. George;Sujata V. Ghate;S. W. Matson;J. Besterman
通讯作者: J. W. George;Sujata V. Ghate;S. W. Matson;J. Besterman
抑制 II 型 DNA 拓扑异构酶的抗肿瘤和抗菌药物的共同作用机制的证据。
DOI: --
发表时间: 1990
期刊: The Journal of biological chemistry
影响因子: --
作者:
Huff,AC;Kreuzer,KN
通讯作者: Kreuzer,KN