Premium
In vitro expansion of DNA triplet repeats with bulge binders and different DNA polymerases
Author(s) -
Ouyang Di,
Yi Long,
Liu Liangliang,
Mu HongTao,
Xi Zhen
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06593.x
Subject(s) - dna , enediyne , dna polymerase , primer (cosmetics) , in vitro , slippage , chemistry , polymerase , dna sequencing , biology , biophysics , microbiology and biotechnology , stereochemistry , biochemistry , materials science , organic chemistry , composite material
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 Che m 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.