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Molecular origins of DNA flexibility: sequence effects on conformational and mechanical properties.

ABSTRACT: A central question in biophysics is whether DNA sequence affects its mechanical properties, which are thought to influence nucleosome positioning and gene expression. Previous attempts to answer this question have been hindered by an inability to resolve DNA structure and dynamics at the base-pair level. Here we use a model to measure the effects of sequence on the stability of DNA under bending. Sequence is shown to influence DNA's flexibility and its ability to form kinks, which arise when certain motifs slide past others to form non-native contacts. A mechanism for nucleosome positioning is proposed in which sequence influences DNA-histone binding by altering the local base-pair-level structure when subject to the curvature necessary for binding.

SUBMITTER: Ortiz V

PROVIDER: S-EPMC3410732 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Molecular origins of DNA flexibility: sequence effects on conformational and mechanical properties.

Ortiz Vanessa V de Pablo Juan J JJ

Physical review letters 20110610 23

A central question in biophysics is whether DNA sequence affects its mechanical properties, which are thought to influence nucleosome positioning and gene expression. Previous attempts to answer this question have been hindered by an inability to resolve DNA structure and dynamics at the base-pair level. Here we use a model to measure the effects of sequence on the stability of DNA under bending. Sequence is shown to influence DNA's flexibility and its ability to form kinks, which arise when cer ...[more]

PMID: 21770550

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Project description:This paper describes effects of the flexibility, length, and branching of side chains on the mechanical properties of low-bandgap semiconducting polymers. The backbones of the polymer chains comprise a diketopyrrolopyrrole (DPP) motif flanked by two furan rings and copolymerized by Stille polycondensation with thiophene (DPP2FT). The side chains of the DPP fall into three categories: linear alkyl (C8, C14, or C16), branched alkyl (ethylhexyl, EH, or hexyldecyl, HD), and linear oligo(ethylene oxide) (EO3, EO4, or EO5). Polymers bearing C8 and C14 side chains are obtained in low yields and thus not pursued. Thermal, mechanical, and electronic properties are plotted against the number of carbon and oxygen atoms in the side chain. We obtain consistent trends in the thermal and mechanical properties for branched alkyl and linear oligo(ethylene oxide) side chains. For example, the glass transition temperature (T g) and elastic modulus decrease with increasing number of carbon and oxygen atoms, whereas the crack-onset strain increases. Among polymers with side chains of 16 carbon and oxygen atoms (C16, HD, and EO5), C16 exhibits the highest T g and the greatest susceptibility to fracture. Hole mobility, as measured in thin-film transistors, appears to be a poor predictor of electronic performance for polymers blended with [60]PCBM in bulk heterojunction (BHJ) solar cells. For example, while EO3 and EO4 exhibit the lowest mobilities (< 10-2 cm2 V-1 s-1) in thin-film transistors, solar cells made using these materials performed the best (efficiency > 2.6%) in unoptimized devices. Conversely, C16 exhibits the highest mobility (≈ 0.2 cm2 V-1 s-1) but produces poor solar cells (efficiency < 0.01%). We attribute the lack of correlation between mobility and power conversion efficiency to unfavorable morphology in the BHJ solar cells. Given the desirable properties measured for EO3 and EO4, the use of flexible oligo(ethylene oxide) side chains is a successful strategy to impart mechanical deformability to organic solar cells, without sacrificing electronic performance.

Project description:In this study we provide the first comprehensive map of DNA conformational flexibility in Saccharomyces cerevisiae complete genome. Flexibility plays a key role in DNA supercoiling and DNA/protein binding, regulating DNA transcription, replication or repair. Specific interest in flexibility analysis concerns its relationship with human genome instability. Enrichment in flexible sequences has been detected in unstable regions of human genome defined fragile sites, where genes map and carry frequent deletions and rearrangements in cancer. Flexible sequences have been suggested to be the determinants of fragile gene proneness to breakage; however, their actual role and properties remain elusive. Our in silico analysis carried out genome-wide via the StabFlex algorithm, shows the conserved presence of highly flexible regions in budding yeast genome as well as in genomes of other Saccharomyces sensu stricto species. Flexibile peaks in S. cerevisiae identify 175 ORFs mapping on their 3'UTR, a region affecting mRNA translation, localization and stability. (TA)n repeats of different extension shape the central structure of peaks and co-localize with polyadenylation efficiency element (EE) signals. ORFs with flexible peaks share common features. Transcripts are characterized by decreased half-life: this is considered peculiar of genes involved in regulatory systems with high turnover; consistently, their function affects biological processes such as cell cycle regulation or stress response. Our findings support the functional importance of flexibility peaks, suggesting that the flexible sequence may be derived by an expansion of canonical TAYRTA polyadenylation efficiency element. The flexible (TA)n repeat amplification could be the outcome of an evolutionary neofunctionalization leading to a differential 3'-end processing and expression regulation in genes with peculiar function. Our study provides a new support to the functional role of flexibility in genomes and a strategy for its characterization inside human fragile sites.

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Molecular origins of DNA flexibility: sequence effects on conformational and mechanical properties.

Publications

Molecular origins of DNA flexibility: sequence effects on conformational and mechanical properties.

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