The P1 phage replication protein RepA contacts an otherwise inaccessible thymine N3 proton by DNA distortion or base flipping

Lyakhov, Ilya; Hengen, Paul N.; Rubens, Denise; Schneider, Thomas D.

doi:10.1093/nar/29.23.4892

Cited by 27 publications

(26 citation statements)

References 32 publications

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“…This effect has been observed in numerous other sequence logos (51,62), and it can be used to precisely assign the location of protein contacts (41,82) (), so the extended −10 pattern further suggests that the T at +4 faces the polymerase through the minor groove. Because position −1 has predominantly T instead of equiprobable A and T (Figure 1), it is unlikely to be bound by a minor groove contact in B-form DNA (62).…”

Section: Discussionmentioning

confidence: 76%

Anatomy of Escherichia coli σ 70 promoters

Shultzaberger

Chen

Lewis

et al. 2006

Nucleic Acids Research

184

261

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Information theory was used to build a promoter model that accounts for the −10, the −35 and the uncertainty of the gap between them on a common scale. Helical face assignment indicated that base −7, rather than −11, of the −10 may be flipping to initiate transcription. We found that the sequence conservation of σ70 binding sites is 6.5 ± 0.1 bits. Some promoters lack a −35 region, but have a 6.7 ± 0.2 bit extended −10, almost the same information as the bipartite promoter. These results and similarities between the contacts in the extended −10 binding and the −35 suggest that the flexible bipartite σ factor evolved from a simpler polymerase. Binding predicted by the bipartite model is enriched around 35 bases upstream of the translational start. This distance is the smallest 5′ mRNA leader necessary for ribosome binding, suggesting that selective pressure minimizes transcript length. The promoter model was combined with models of the transcription factors Fur and Lrp to locate new promoters, to quantify promoter strengths, and to predict activation and repression. Finally, the DNA-bending proteins Fis, H-NS and IHF frequently have sites within one DNA persistence length from the −35, so bending allows distal activators to reach the polymerase.

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Section: Discussionmentioning

confidence: 76%

Anatomy of Escherichia coli σ 70 promoters

Shultzaberger

Chen

Lewis

et al. 2006

Nucleic Acids Research

184

261

View full text Add to dashboard Cite

show abstract

“…Because of the high energy cost for breaking H-bonds in spontaneous base opening for DNA and RNA [46,47], base flipping is usually activated by strong protein-DNA interactions for DNA strand separation and unwinding during DNA replication or transcription [48][49][50]. Therefore, the drug-induced base flipping would disrupt the normal protein-DNA/RNA interactions for their normal function, which may lead to the death of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Early stage intercalation of doxorubicin to DNA fragments observed in molecular dynamics binding simulations

Lei

Wang

2012

Journal of Molecular Graphics and Modelling

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“…This construct has been shown to form tight hairpins (6,39). All oligos were synthesized carrying a 5′-biotin tag (Synthegen, LLC) to allow immobilization of the oligos onto NeutrAvidin (NA)-coated sensor chips (B1 chips, Biacore Inc.).…”

Section: Methodsmentioning

confidence: 99%

Correlation between binding rate constants and individual information of E. coli Fis binding sites

Shultzaberger

Roberts

Lyakhov

et al. 2007

Nucleic Acids Research

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Individual protein binding sites on DNA can be measured in bits of information. This information is related to the free energy of binding by the second law of thermodynamics, but binding kinetics appear to be inaccessible from sequence information since the relative contributions of the on- and off-rates to the binding constant, and hence the free energy, are unknown. However, the on-rate could be independent of the sequence since a protein is likely to bind once it is near a site. To test this, we used surface plasmon resonance and electromobility shift assays to determine the kinetics for binding of the Fis protein to a range of naturally occurring binding sites. We observed that the logarithm of the off-rate is indeed proportional to the individual information of the binding sites, as predicted. However, the on-rate is also related to the information, but to a lesser degree. We suggest that the on-rate is mostly determined by DNA bending, which in turn is determined by the sequence information. Finally, we observed a break in the binding curve around zero bits of information. The break is expected from information theory because it represents the coding demarcation between specific and nonspecific binding.

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The P1 phage replication protein RepA contacts an otherwise inaccessible thymine N3 proton by DNA distortion or base flipping

Cited by 27 publications

References 32 publications

Anatomy of Escherichia coli σ 70 promoters

Anatomy of Escherichia coli σ 70 promoters

Early stage intercalation of doxorubicin to DNA fragments observed in molecular dynamics binding simulations

Correlation between binding rate constants and individual information of E. coli Fis binding sites

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