Structural studies of butadiene-derived DNA adducts

Abstract

This dissertation involved the structural investigations of butadiene-derived N6,N6-deoxycytosine intrastrand cross-linked adduct and N3-deoxyuridine adducts in DNA by NMR or X-ray crystallography, respectively. Solution structure of the N6,N6-deoxycytosine intrastrand cross-link indicated that the butadiene lesion was oriented in the major groove and existed in two conformations with formation of different hydrogen bonds between the beta-OH and the 5' base pair T16 O4 or the 3' base pair T17 O4. Crystal structures of binary Dpo4-DNA complexes and ternary Dpo4-DNA-d(d)NTP complexes containing BD-N3-deoxyuridine adducts with the Sulfolobus solfataricus DNA Polymerase IV (Dpo4) were determined. This is the first time to study Dpo4 complexes containing non-planar adducts in the template. The resulted non-productive crystal structures suggested that steric effect plays a significant role in bypass of damaged DNA by trans-lesion polymerase Dpo4.