Selective inhibition of DNA polymerase epsilon by phosphatidylinositol.

Selective inhibition of DNA polymerase epsilon by phosphatidylinositol.
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磷脂酰肌醇选择性抑制DNA聚合酶ε。

DOI:
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发表时间:
1995
期刊:
Journal of Biochemistry (Tokyo)
影响因子:
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通讯作者:
S. Yoshida
S. Yoshida
中科院分区:
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文献类型:
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作者:
M. Shoji;S. Izuta;K. Tamiya‐Koizumi;M. Suzuki;S. Yoshida

文献摘要

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我们研究了各种磷脂对小牛胸腺DNA聚合酶α、δ和ε的DNA合成反应的影响。在这三种酶中,DNA聚合酶ε对酸性磷脂最敏感,即磷脂酰肌醇(PI)、磷脂酰肌醇4-单磷酸(PIP)、磷脂酰丝氨酸(PS)、磷脂酸(PA)和心磷脂(CAR)。在这些酸性磷脂中,PI(来自牛肝)特别令人感兴趣,因为它对 DNA 聚合酶 ε 的抑制作用比 DNA 聚合酶 α 和 δ 强得多。 PI 对 DNA 聚合酶 epsilon 的抑制作用与 DNA 模板引物竞争性,与 dTTP 底物非竞争性。 Ki 值估计为 16 microM。这些结果表明,来自牛肝脏的PI可以作为DNA聚合酶ε的特异性抑制剂来分析其在DNA复制中的作用。有趣的是,从具有不同脂肪酸组成的大豆中分离的PI不仅抑制DNA聚合酶ε,而且抑制DNA聚合酶α。
We studied the effects of various phospholipids on the DNA synthesizing reactions by calf thymus DNA polymerases alpha, delta, and epsilon. Of these three enzymes, DNA polymerase epsilon was most sensitive to acidic phospholipids, i.e., phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP), phosphatidylserine (PS), phosphatidic acid (PA), and cardiolipin (CAR). Of these acidic phospholipids, PI (from bovine liver) is of special interest because it inhibited DNA polymerase epsilon much strongly than DNA polymerase alpha and delta. The inhibition of DNA polymerase epsilon by PI was competitive with the DNA template-primer and was noncompetitive with dTTP substrate. The Ki value was estimated to be 16 microM. These results indicate that PI from bovine liver can be used as a specific inhibitor for DNA polymerase epsilon to analyze its role in DNA replication. Interestingly, the PI isolated from soybean, which has a different fatty acid composition, inhibited not only DNA polymerase epsilon but also DNA polymerase alpha.