High affinity interaction of mammalian DNA topoisomerase I with short single- and double-stranded oligonucleotides
- 作者：Nevinsky ; Georgy A. ; Bugreev ; Dmitry V. ; Buneva ; Valentina N. ; Yasui ; Yoshihiro ; Nishizawa ; Miwako ; et. al.
- 关键词：DNA topoisomerase I ; Oligodeoxynucleotide ; Competitive inhibition
- 刊名：FEBS Letters
- 出版年：1995
- 期刊代码：70_00145793
- 类别：bio
- 出版时间：July 10, 1995
- 卷：368
- 期：1
- 页码：97-100
- 文件大小：305 K
摘要
The interaction of DNA topoisomerase I (topo I) with a set of single- and double-stranded oligonucleotides containing 5-27 mononucleotides was investigated. All single- and double-stranded oligonucleotides were found to inhibit competitively the supercoiled DNA relaxation reaction catalyzed by topo I. The enzyme affinity for specific sequence pentanucleotides of the scissile (GACTT, Ki = 2 μM) and non-cleaved chain (AAGTC, Ki = 110 μM) is about 2-4 orders of magnitude higher than that for non-specific oligonucleotides. This specific sequence affinity increases in several cases: lengthening of single-stranded oligonucleotides, formation of stable duplexes between complementary oligonucleotides and preincubation of the enzyme with ligands before addition of supercoiled DNA. We assume that oligonucleotides having a high affinity to the enzyme can offer a unique opportunity for rational design of topoisomerase-targeting drugs.