ACIDIC PHOSPHOLIPIDS DIRECTLY INHIBIT DNA-BINDING OF MAMMALIAN DNA TOPOISOMERASE-I

被引:31
作者
TAMURA, H [1 ]
IKEGAMI, Y [1 ]
ONO, K [1 ]
SEKIMIZU, K [1 ]
ANDOH, T [1 ]
机构
[1] UNIV TOKYO,FAC PHARMACEUT SCI,BUNKYO KU,TOKYO 113,JAPAN
关键词
Phospholipid; Topoisomerase I;
D O I
10.1016/0014-5793(90)80658-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. © 1990.
引用
收藏
页码:151 / 154
页数:4
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