Single base DNA lesions and mismatches, such as T:G mismatches, uracil, dihydrouracil, and 1-N6-ethenoadenine, correlate with apoptosis, aging, carcinogenesis, mutagenesis and are typically fixed by base excision repair. These lesions and mismatches were studied using the Dickerson-Drew Dodecamer, [5`-(dCGCGAATTCGCG)-3`], a small sequence with robust information available to compare to single base modified variations. The importance of the neighboring nucleobases in the affinity of the repair enzyme for T:G mismatches is studied using a short, non-palindromic strand. The dynamic properties were investigated by 1H-31P HSQC. The 31P chemical shifts of the phosphodiester backbone correlate with BI and BII, the primary conformations of B-DNA and its thermodynamics of the BI-BII equilibrium. The work shows significant, local changes in the %BII and thermodynamic properties due to presence of a mismatch or lesion, which may facilitate the initial step of enzyme recognition in the repair mechanism.

Sequence-dependent investigation of T:G mismatches in DNA

ACS Spring 2022

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