Deoxyadenosine-deoxycytidine pairing in the d(C-G-C-G-A-A-T-T-C-A-C-G) duplex: conformation and dynamics at and adjacent to the dA.cntdot.dC mismatch site

Authors:
  • DPDinshaw J. Patel
    Dinshaw J. Patel
  • SKSharon A. Kozlowski
    Sharon A. Kozlowski
  • SISatoshi Ikuta
    Satoshi Ikuta
  • KIKeiichi Itakura
    Keiichi Itakura
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Abstract
Deoxyadenosine-deoxycytidine pairing at symmetrically related dA X dC mismatch sites in the d(C1-G2-C3-G4-A5-A6-T6-T5-C4-A3-C2-G1) self-complementary duplex (henceforth called 12-mer AC) has been investigated by proton and phosphorus NMR studies in aqueous solution. We demonstrate that base pairing is maintained on either side of the mismatch site in the 12-mer AC duplex at low temperature. The proton chemical shifts and NOE measurements rule out models in which the H-2 proton of adenosine at the mismatch site is stacked over adjacent dG X dC base pairs. A comparison of the hydrogen-exchange kinetics in the d(C-G-C-G-A-A-T-T-C-G-C-G) duplex (henceforth called 12-mer) with standard dG X dC base pairs at position 3 from either end with the 12-mer AC duplex, which contains dA X dC mismatches at these positions, demonstrates kinetic destabilization at dG X dC base pair 4 adjacent to the mismatch site and at dA X dT base pairs 5 and 6 far from this site. This contrasts with previous hydrogen-exchange studies on the 12-mer GT and 12-mer GA duplexes where the kinetic destabilization was localized to base pair 4, which is adjacent to the mispairing site. The melting temperature of the 12-mer AC duplex in 0.1 M phosphate is approximately 30 degrees C lower than the corresponding value for the 12-mer duplex.(ABSTRACT TRUNCATED AT 250 WORDS)