Abstract
The solution structure of the DNA duplex d(C1G2C3G4A5D6A7C8G9C10C11)-d (G22C21G20C19T18A17T16G15C14G13-G12), with D indicating a deoxyribose aldehyde abasic site and numbering from 5' to 3', has been determined by the combined use of NMR and restrained molecular dynamics. The 31P and 31P-1H correlation data indicate that the backbones of these duplex DNAs are regular. One- and two-dimensional 1H NMR data indicate that the duplexes are right-handed and B-form. Conformational changes due to the presence of the abasic site extends to the base pairs adjacent to the lesion site with the local conformation of the DNA being dependent on whether the abasic site is in the alpha or beta configuration. When the sugar of the abasic site is in the beta configuration the deoxyribose is within the helix, whereas when the sugar is in the alpha configuration the deoxyribose is out of the helix. The base of residue A17 in the position opposite the abasic site is predominantly stacked in the helix in both cases. A water molecule can apparently form a hydrogen bond bridge between the beta abasic site and A17.
Highlights
The abasic site is not a chemically unique species but is an equilibrium mixture of four forms (8 –10)
When a mature nerve cell is infected by herpes, pseudorabies or other virus DNA repair is activated by repair enzymes, including uracil glycosylase, coded by the virus (28 –30)
There may be special features associated with dA interacting with the abasic site with these physical properties determining to the dA preference which occurs during the rate determining step in the polymerase reaction
Summary
The abasic site is not a chemically unique species but is an equilibrium mixture of four forms (8 –10). There have been a number of studies of DNA duplexes containing analogues of the naturally occurring abasic site [43,44,45,46]. The refined solution state structures of duplex DNAs containing abasic sites may be useful for comparison with those generated by anti-tumor and other drugs.
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