Base-Pair Mismatch Can Destabilize Small DNA Loops through Cooperative Kinking

Jeong, Jiyoun; Kim, Harold D.

doi:10.1103/physrevlett.122.218101

Cited by 18 publications

(24 citation statements)

References 40 publications

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“…1 ). The looped population could comprise closed structures with alternate shapes and basepairing geometries 10 , 11 ( Extended Data Fig. 2 ).…”

Section: Dna Mechanics In High Throughputmentioning

confidence: 99%

“…Other non-canonical geometries may also be possible, such as a U-turn geometry, where the sticky overhangs interact via reverse Watson-Crick basepairing in a parallel stranded configuration. Conventional Watson-Crick base pairing between the overhangs, but in a geometry similar to the U-turn configuration, has been achieved in the past (hairpin loop 10 ). Presence of mismatches or transient defects in the duplex region may influence whether such a geometry is preferred over the teardrop or smooth configuration 10 .…”

Section: Extended Datamentioning

confidence: 99%

“…Conventional Watson-Crick base pairing between the overhangs, but in a geometry similar to the U-turn configuration, has been achieved in the past (hairpin loop 10 ). Presence of mismatches or transient defects in the duplex region may influence whether such a geometry is preferred over the teardrop or smooth configuration 10 . Because all members of various libraries in our study used the same overhang sequences, relative differences between them in their looping kinetics are unlikely to be affected by a potential conformational heterogeneity of the looped state.…”

Section: Extended Datamentioning

confidence: 99%

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Measuring DNA mechanics on the genome scale

Basu

Bobrovnikov

Qureshi

et al. 2020

Nature

118

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Mechanical deformations of DNA such as bending are ubiquitous and implicated in diverse cellular functions 1 . However, the lack of high-throughput tools to directly measure the mechanical properties of DNA limits our understanding of whether and how DNA sequences modulate DNA mechanics and associated chromatin transactions genome-wide. We developed an assay called loop-seq to measure the intrinsic cyclizability of DNA – a proxy for DNA bendability – in high throughput. We measured the intrinsic cyclizabilities of 270,806 50 bp DNA fragments that span the entire length of S. cerevisiae chromosome V and other genomic regions, and also include random sequences. We discovered sequence-encoded regions of unusually low bendability upstream of Transcription Start Sites (TSSs). These regions disfavor the sharp DNA bending required for nucleosome formation and are co-centric with known Nucleosome Depleted Regions (NDRs). We show biochemically that low bendability of linker DNA located about 40 bp away from a nucleosome edge inhibits nucleosome sliding into the linker by the chromatin remodeler INO80. The observation explains how INO80 can create promoter-proximal nucleosomal arrays in the absence of any other factors 2 by reading the DNA mechanical landscape. We show that chromosome wide, nucleosomes are characterized by high DNA bendability near dyads and low bendability near the linkers. This contrast increases for nucleosomes deeper into gene bodies, suggesting that DNA mechanics plays a previously unappreciated role in organizing nucleosomes far from the TSS, where nucleosome remodelers predominate. Importantly, random substitution of synonymous codons does not preserve this contrast, suggesting that the evolution of codon choice has been impacted by selective pressure to preserve sequence-encoded mechanical modulations along genes. We also provide evidence that transcription through the TSS-proximal nucleosomes is impacted by local DNA mechanics. Overall, this first genome-scale map of DNA mechanics hints at a ‘mechanical code’ with broad functional implications.

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“…1 ). The looped population could comprise closed structures with alternate shapes and basepairing geometries 10 , 11 ( Extended Data Fig. 2 ).…”

Section: Dna Mechanics In High Throughputmentioning

confidence: 99%

Section: Extended Datamentioning

confidence: 99%

Section: Extended Datamentioning

confidence: 99%

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Measuring DNA mechanics on the genome scale

Basu

Bobrovnikov

Qureshi

et al. 2020

Nature

118

View full text Add to dashboard Cite

show abstract

“…2). The looped population could comprise closed structures with alternate shapes and basepairing geometries 10,11 (Extended Data Fig. 1).…”

mentioning

confidence: 99%

Measuring DNA mechanics on the genome scale

Basu

Bobrovnikov

Qureshi

et al. 2020

Preprint

View full text Add to dashboard Cite

Mechanical deformations of DNA such as bending are ubiquitous and implicated in diverse cellular functions. However, the lack of high-throughput tools to directly measure the mechanical properties of DNA limits our understanding of whether and how DNA sequences modulate DNA mechanics and associated chromatin transactions genome-wide. We developed an assay called loop-seq to measure the intrinsic cyclizability of DNA, a proxy for DNA bendability, in high throughput. We measured the intrinsic cyclizabilities of 270,806 50 bp DNA fragments that span the entire length of S. cerevisiae chromosome V and other genomic regions, and also include random sequences. We discovered sequence-encoded regions of unusually low bendability upstream of Transcription Start Sites (TSSs). These regions disfavor the sharp DNA bending required for nucleosome formation and are co-centric with known Nucleosome Depleted Regions (NDRs). We show biochemically that low bendability of linker DNA located about 40 bp away from a nucleosome edge inhibits nucleosome sliding into the linker by the chromatin remodeler INO80. The observation explains how INO80 can create promoter-proximal nucleosomal arrays in the absence of any other factors by reading the DNA mechanical landscape. We show that chromosome wide, nucleosomes are characterized by high DNA bendability near dyads and low bendability near the linkers. This contrast increases for nucleosomes deeper into gene bodies, suggesting that DNA mechanics plays a previously unappreciated role in organizing nucleosomes far from the TSS, where nucleosome remodelers predominate. Importantly, random substitution of synonymous codons does not preserve this contrast, suggesting that the evolution of codon choice has been impacted by selective pressure to preserve sequence-encoded mechanical modulations along genes. We also provide evidence that transcription through the TSS-proximal nucleosomes is impacted by local DNA mechanics. Overall, this first genome-scale map of DNA mechanics hints at a mechanical code with broad functional implications.

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“…Interesting questions include whether and how the relaxed species form secondary or tertiary structures, and where the interacting ions and molecules reside. Advanced single-molecule fluorescence techniques, such as single-molecule fluorescence resonance energy transfer (FRET), are expected to advance such understanding, as shown by the beautiful, pioneering work by several groups in this direction [83,[102][103][104][105][106].…”

Section: Patentsmentioning

confidence: 99%

Bent DNA Bows as Sensing Amplifiers for Detecting DNA-Interacting Salts and Molecules

Freeland

Zhang

Wang

et al. 2020

Sensors

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Due to the central role of DNA, its interactions with inorganic salts and small organic molecules are important. For example, such interactions play important roles in various fundamental cellular processes in living systems and are involved in many DNA-damage related diseases. Strategies to improve the sensitivity of existing techniques for studying DNA interactions with other molecules would be appreciated in situations where the interactions are too weak. Here we report our development and demonstration of bent DNA bows for amplifying, sensing, and detecting the interactions of 14 inorganic salts and small organic molecules with DNA. With the bent DNA bows, these interactions were easily visualized and quantified in gel electrophoresis, which were difficult to measure without bending. In addition, the strength of the interactions of DNA with the various salts/molecules were quantified using the modified Hill equation. This work highlights the amplification effects of the bending elastic energy stored in the DNA bows and the potential use of the DNA bows for quantitatively measuring DNA interactions with small molecules as simple economic methods; it may also pave the way for exploiting the bent DNA bows for other applications such as screening DNA-interacting molecules and drugs.

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Base-Pair Mismatch Can Destabilize Small DNA Loops through Cooperative Kinking

Cited by 18 publications

References 40 publications

Measuring DNA mechanics on the genome scale

Measuring DNA mechanics on the genome scale

Measuring DNA mechanics on the genome scale

Bent DNA Bows as Sensing Amplifiers for Detecting DNA-Interacting Salts and Molecules

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