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Acidic phospholipids directly inhibit DNA binding of mammalian DNA topoisomerase I
Author(s) -
Tamura Hiro-omi,
Ikegami Yoji,
Ono Katsuhiro,
Sekimizu Kazuhisa,
Andoh Toshiwo
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)80658-6
Subject(s) - topoisomerase , phosphatidylethanolamine , camptothecin , biochemistry , enzyme , dna , phosphatidylglycerol , phospholipid , chemistry , biology , microbiology and biotechnology , membrane , phosphatidylcholine
Inhibition of mammalian DNA topoisomerase I by phospholipids was investigated using purified enzyme. Acidic phospholipids inhibited the DNA relaxation activity of topoisomerase I whereas neutral phospholipid, phosphatidylethanolamine, did not. Accumulation of a protein‐DNA cleavable complex, an intermediate which is known to accumulate upon inhibition by a specific inhibitor camptothecin, did not occur. The filter binding assay revealed that the DNA binding activity of the enzyme was inhibited by acidic phospholipids. Moreoever, direct binding of phosphatidylglycerol to topoisomerase I was demonstrated. These results indicated that the inhibitory effect of acidic phospholipids on topoisomerase I was due to the loss of the DNA binding of the enzyme as a result of direct interaction between phospholipids and the enzyme.