Selective Inhibition of DNA Polymerase ε by Phosphatidylinositol

• Published in: Journal of biochemistry (Tokyo) Vol. 117; no. 5; pp. 1095 - 1099
• Main Authors: Shoji-Kawaguchi, Mami, Izuta, Shunji, Tamiya-Koizumi, Keiko, Suzuki, Motoshi, Yoshida, Shonen
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.1995
• Subjects: Animals; Cattle; DNA Polymerase II - antagonists & inhibitors; DNA Polymerase III; DNA polymerase α; DNA polymerase δ; DNA polymerase ε; Glycine max - chemistry; inhibitor; Liver - chemistry; Nucleic Acid Synthesis Inhibitors; phosphatidylinositol; Phosphatidylinositols - isolation & purification; Phosphatidylinositols - pharmacology; Phospholipids - pharmacology
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/oxfordjournals.jbchem.a124812

We studied the effects of various phoapholipids on the DNA synthesizing reactions by calf thymus DNA polymerases α, δ, and ε. Of these three enzymes, DNA polymerase ε 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 ε much more strongly than DNA polymerase α and δ. The inhibition of DNA polymerase ε by PI was competitive with the DNA template-primer and was noncompetitive with dTTP substrate. The K1 value was estimated to be 16 μM. These results indicate that PI from bovine liver can be used as a specific inhibitor for DNA polymerase ε 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 ε but also DNA polymerase α.