Triplex-forming oligonucleotides trigger conformation changes of a target hairpin sequence

被引:6
作者
Brossalina, E
Demchenko, E
Demchenko, Y
Vlassov, V
Toulme, JJ
机构
[1] UNIV BORDEAUX 2, IFR PATHOL INFECT, INSERM U386, F-33076 BORDEAUX, FRANCE
[2] RUSSIAN ACAD SCI, INST BIOORGAN CHEM, SIBERIAN DIV, NOVOSIBIRSK 630090, RUSSIA
关键词
D O I
10.1093/nar/24.17.3392
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
We used a DNA duplex formed between the 5' end of a 69mer (69T) and an 11mer (OL7) as a substrate for BamHI. The former oligonucleotide folds into a hairpin structure, the stem of which contains a stretch of pyrimidines in one strand and consequently a stretch of purines in the other strand. The oligomer 69T was used as a target for complementary oligodeoxypyrimidines made of 10 nt (OL1), 16 nt (OL5) or 26 nt (OL2) which can engage the same 10 pyrimidine-purine-pyrimidine triplets with the 69T hairpin stem. Although the binding site of OL7 did not overlap that OL1, OL2 or OL5, the BamHI activity on 69T-OL7 complexes was drastically modified in the presence of these triplex-forming oligomers: OL1 abolished the cleavage by BamHI whereas OL5 and OL2 strongly increased it. Using footprinting assays and point-mutated oligonucleotides we demonstrated that these variations were due to different conformations of the 69T-OL7 complex induced by the binding of oligomers OL1, OL2 or OL5. Therefore, oligonucleotides can act as structural switchers, offering one additional mode for modulating gene expression.
引用
收藏
页码:3392 / 3398
页数:7
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