In vitro expansion of DNA triplet repeats with bulge binders and different DNA polymerases

被引：8
作者：
Di Ouyang
Yi, Long
Liu, Liangliang
Mu, Hong-Tao
Xi, Zhen [1 ]
机构：
[1] Nankai Univ, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China
来源：
FEBS JOURNAL | 2008年 / 275卷 / 18期
基金：
中国国家自然科学基金;
关键词：
bulge binder; DNA polymerase; DNA slippage; drug-DNA interaction; repeat sequences;
D O I：
10.1111/j.1742-4658.2008.06593.x
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：
The expansion of DNA repeat sequences is associated with many genetic diseases in humans. Simple bulge DNA structures have been implicated as intermediates in DNA slippage within the DNA repeat regions. To probe the possible role of bulged structures in DNA slippage, we designed and synthesized a pair of simple chiral spirocyclic compounds [Xi Z, Ouyang D & Mu HT (2006) Bioorg Med Chem Lett 16, 1180-1184], DDI-1A and DDI-1B, which mimic the molecular architecture of the enediyne antitumor antibiotic neocarzinostatin chromophore. Both compounds strongly stimulated slippage in various DNA repeats in vitro. Enhanced slippage synthesis was found to be synchronous for primer and template. CD spectra and UV thermal stability studies supported the idea that DDI-1A and DDI-1B exhibited selective binding to the DNA bulge and induced a significant conformational change in bulge DNA. The proposed mechanism for the observed in vitro expansion of long DNA is discussed.
引用
收藏
页码：4510 / 4521
页数：12
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