Effect of Base Pair A/C and G/T Mismatches on the Thermal Stabilities of DNA Oligomers That Form B-Z Junctions
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- 作者：Ebenezer O. Otokiti and and Richard D. Sheardy
- 刊名：Biochemistry
- 出版年：1997
- 出版时间：September 23, 1997
- 年：1997
- 卷：36
- 期：38
- 页码：11419 - 11427
- 全文大小：194K
- 年卷期：v.36,no.38(September 23, 1997)
- ISSN：1520-4995
文摘
The thermal stabilities and structures of B-Z junctionforming DNA duplexes possessingA/C or G/T base pair mismatches were compared to those of correspondingduplexes possessing perfectmatched base pairs. The upper strands of the duplexes have ageneralized sequence 5'-(5meCG)-LMN-GACTG-3', where L stands for A or G while M and N are permutations ofpyrimidines. The lowerstrands were either complementary or were such as to create an A/C orG/T mismatch at the positioncorresponding to L, M, or N. Optical melting and circulardichroism studies were used to investigate thethermal stabilities and structures of both the mismatched base pair andthe perfect matched base pairduplexes. Incorporating mismatched A/C or G/T base pairs did notnoticeably affect the conformationsof the duplexes in 115 mM Na+ but resulted in perturbedB-Z conformations at 4.5 M Na+. Foranymismatched base pair duplex, the B-DNA domain of the hybrid B-Zstructure formed at 4.5 M Na+ issignificantly perturbed while the Z-DNA domain is less perturbed by thepresence of the mismatchedbase pairs. The presence of a mismatch destabilizes a duplexrelative to the perfect matched base pairduplex by 1.7-10.0 kcal/mol depending upon position of the mismatch,type of mismatch base pairinvolved, and Na+ concentration. The thermodynamicdestabilization of a mismatched base pair duplexrelative to the perfect matched base pair duplex arises fromperturbations in nearest neighbor interactionsand hydrogen bonding. In general, we observed that theincorporation of an A/C or G/T base pair mismatchin place of a perfect matched base pair at or near a B-Z junctionresults in a relatively large change inenthalpy and entropy to produce a significant change in the free energyof the duplex to single strandtransition. At 4.5 M Na+, where the duplexes possessperturbed B-Z junctions, the farther away fromthe junction that the mismatch is, the greater the extent of thedestabilization.