Dataset Information

DNA bending propensity in the presence of base mismatches: implications for DNA repair.

ABSTRACT: DNA bending is believed to facilitate the initial recognition of the mismatched base for repair. The repair efficiencies are dependent on both the mismatch type and neighboring nucleotide sequence. We have studied bending of several DNA duplexes containing canonical matches: A:T and G:C; various mismatches: A:A, A:C, G:A, G:G, G:T, C:C, C:T, and T:T; and a bis-abasic site: X:X. Free-energy profiles were generated for DNA bending using umbrella sampling. The highest energetic cost associated with DNA bending is observed for canonical matches while bending free energies are lower in the presence of mismatches, with the lowest value for the abasic site. In all of the sequences, DNA duplexes bend toward the major groove with widening of the minor groove. For homoduplexes, DNA bending is observed to occur via smooth deformations, whereas for heteroduplexes, kinks are observed at the mismatch site during strong bending. In general, pyrimidine:pyrimidine mismatches are the most destabilizing, while purine:purine mismatches lead to intermediate destabilization, and purine:pyrimidine mismatches are the least destabilizing. The ease of bending is partially correlated with the binding affinity of MutS to the mismatch pairs and subsequent repair efficiencies, indicating that intrinsic DNA bending propensities are a key factor of mismatch recognition.

SUBMITTER: Sharma M

PROVIDER: S-EPMC3676302 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

DNA bending propensity in the presence of base mismatches: implications for DNA repair.

Sharma Monika M Predeus Alexander V AV Mukherjee Shayantani S Feig Michael M

The journal of physical chemistry. B 20130510 20

DNA bending is believed to facilitate the initial recognition of the mismatched base for repair. The repair efficiencies are dependent on both the mismatch type and neighboring nucleotide sequence. We have studied bending of several DNA duplexes containing canonical matches: A:T and G:C; various mismatches: A:A, A:C, G:A, G:G, G:T, C:C, C:T, and T:T; and a bis-abasic site: X:X. Free-energy profiles were generated for DNA bending using umbrella sampling. The highest energetic cost associated with ...[more]

PMID: 23621762

Similar Datasets

Project description:BACKGROUND: The high binding specificity of short 10 to 30 mer oligonucleotide probes enables single base mismatch (MM) discrimination and thus provides the basis for genotyping and resequencing microarray applications. Recent experiments indicate that the underlying principles governing DNA microarray hybridization - and in particular MM discrimination - are not completely understood. Microarrays usually address complex mixtures of DNA targets. In order to reduce the level of complexity and to study the problem of surface-based hybridization with point defects in more detail, we performed array based hybridization experiments in well controlled and simple situations. RESULTS: We performed microarray hybridization experiments with short 16 to 40 mer target and probe lengths (in situations without competitive hybridization) in order to systematically investigate the impact of point-mutations - varying defect type and position - on the oligonucleotide duplex binding affinity. The influence of single base bulges and single base MMs depends predominantly on position - it is largest in the middle of the strand. The position-dependent influence of base bulges is very similar to that of single base MMs, however certain bulges give rise to an unexpectedly high binding affinity. Besides the defect (MM or bulge) type, which is the second contribution in importance to hybridization affinity, there is also a sequence dependence, which extends beyond the defect next-neighbor and which is difficult to quantify. Direct comparison between binding affinities of DNA/DNA and RNA/DNA duplexes shows, that RNA/DNA purine-purine MMs are more discriminating than corresponding DNA/DNA MMs. In DNA/DNA MM discrimination the affected base pair (C.G vs. A.T) is the pertinent parameter. We attribute these differences to the different structures of the duplexes (A vs. B form). CONCLUSION: We have shown that DNA microarrays can resolve even subtle changes in hybridization affinity for simple target mixtures. We have further shown that the impact of point defects on oligonucleotide stability can be broken down to a hierarchy of effects. In order to explain our observations we propose DNA molecular dynamics - in form of zipping of the oligonucleotide duplex - to play an important role.

Dataset Information

DNA bending propensity in the presence of base mismatches: implications for DNA repair.

Publications

DNA bending propensity in the presence of base mismatches: implications for DNA repair.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets