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Structure, dynamics, and thermodynamics of mismatched DNA oligonucleotide duplexes d(CCCAGGG)/sub 2/ and d(CCCTGGG)/sub 2/

Journal Article · · Biochemistry; (United States)
OSTI ID:5940917

The structures and hydrogen exchange properties of the mismatched DNA oligonucleotide duplexes d(CCCAGGG)/sub 2/ and d(CCCTGGG)/sub 2/ have been studied by high-resolution nuclear magnetic resonance. Both the adenine-adenine and thymine-thymine mismatches are intercalated in the duplexes. The structures of these self-complementary duplexes are symmetric, with the two strands in equivalent positions. The evidence indicates that these mismatches are not stably hydrogen bonded. The mismatched bases in both duplexes are in the anti conformation. The mismatched thymine nucleotide in d(CCCTGGG)/sub 2/ is intercalated in the duplex with very little distortion of the bases or sugar-phosphate backbone. In contrast, the bases of the adenine-adenine mismatch in d(CCCAGGG)/sub 2/ must tilt and push apart to reduce the overlap of the amino groups. The thermodynamic data show that the T-T mismatch is less destabilizing than the A-A mismatch when flanked by C-G base pairs in this sequence, in contrast to their approximately equal stabilities when flanked by A-T base pairs in the sequence d(CAAAXAAAG-CTTTYTTTG) where X and Y = A, C, G, and T. Although the mechanism cannot be determined conclusively from the limited data obtained, exchange of the imino protons with solvent in these destabilized heteroduplexes appears to occur by a cooperative mechanism in which half the helix dissociates.

Research Organization:
Univ. of California, Berkeley
DOE Contract Number:
AS03-82ER60090
OSTI ID:
5940917
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:13; ISSN BICHA
Country of Publication:
United States
Language:
English