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8
DISCUSSION
0
null
null
17,135,188
null
Moreover, this study describes a combination of techniques which represent easy to handle tools suitable for a detailed analysis of carrier-mediated delivery of therapeutically interesting nucleic acid molecules, which eventually may lead to considerably improved delivery.
null
273
3,600
0
false
null
null
Moreover, this study describes a combination of techniques which represent easy to handle tools suitable for a detailed analysis of carrier-mediated delivery of therapeutically interesting nucleic acid molecules, which eventually may lead to considerably improved delivery.
true
true
true
true
true
599
0
INTRODUCTION
1
1
[ "b1", "b2" ]
16,835,309
pmid-13718526|pmid-15950160|pmid-7824935|pmid-13130131|pmid-15155821|pmid-1861724|pmid-16407332
Since its first description, formulated more than 40 years ago (1), the Lac operon has represented a crucial system for understanding basic mechanisms of gene regulation and the response of living organisms to changes in the environment.
[ "1", "2" ]
237
3,601
1
false
Since its first description, formulated more than 40 years ago, the Lac operon has represented a crucial system for understanding basic mechanisms of gene regulation and the response of living organisms to changes in the environment.
[ "1" ]
Since its first description, formulated more than 40 years ago, the Lac operon has represented a crucial system for understanding basic mechanisms of gene regulation and the response of living organisms to changes in the environment.
true
true
true
true
true
600
0
INTRODUCTION
1
1
[ "b1", "b2" ]
16,835,309
pmid-13718526|pmid-15950160|pmid-7824935|pmid-13130131|pmid-15155821|pmid-1861724|pmid-16407332
Over the past decades, a wealth of information on the molecular structure and mechanisms of this system has been provided by genetics, biochemistry and structural biology, leading to a detailed picture of the genetic elements of the Lac operon, the atomic structure of the Lac repressor (LacI) and the kinetics and therm...
[ "1", "2" ]
353
3,602
0
false
Over the past decades, a wealth of information on the molecular structure and mechanisms of this system has been provided by genetics, biochemistry and structural biology, leading to a detailed picture of the genetic elements of the Lac operon, the atomic structure of the Lac repressor (LacI) and the kinetics and therm...
[]
Over the past decades, a wealth of information on the molecular structure and mechanisms of this system has been provided by genetics, biochemistry and structural biology, leading to a detailed picture of the genetic elements of the Lac operon, the atomic structure of the Lac repressor (LacI) and the kinetics and therm...
true
true
false
true
false
600
0
INTRODUCTION
1
1
[ "b1", "b2" ]
16,835,309
pmid-13718526|pmid-15950160|pmid-7824935|pmid-13130131|pmid-15155821|pmid-1861724|pmid-16407332
[for a recent review see (2)].
[ "1", "2" ]
30
3,603
0
false
.
[ "for a recent review see (2)" ]
.
false
false
true
true
false
600
1
INTRODUCTION
1
3
[ "b3", "b4", "b5", "b6", "b7", "b10", "b11", "b12" ]
16,835,309
pmid-1579106|pmid-4601586|pmid-430569|pmid-10581237|pmid-6272277|pmid-15809441|NA|pmid-8571451|NA|pmid-16303869|pmid-3293588|pmid-8628994|pmid-4601586|pmid-430569|pmid-9336213|pmid-15783356|pmid-14500788
One fundamental aspect, emerging from several studies, is that LacI can bind simultaneously to two operators on the DNA (normally the primary operator and a second sequence, termed a pseudooperator), forming a loop in the intervening sequence.
[ "3", "4", "5", "6", "7", "10", "11", "12" ]
243
3,604
0
false
One fundamental aspect, emerging from several studies, is that LacI can bind simultaneously to two operators on the DNA (normally the primary operator and a second sequence, termed a pseudooperator), forming a loop in the intervening sequence.
[]
One fundamental aspect, emerging from several studies, is that LacI can bind simultaneously to two operators on the DNA (normally the primary operator and a second sequence, termed a pseudooperator), forming a loop in the intervening sequence.
true
true
true
true
true
601
1
INTRODUCTION
1
3
[ "b3", "b4", "b5", "b6", "b7", "b10", "b11", "b12" ]
16,835,309
pmid-1579106|pmid-4601586|pmid-430569|pmid-10581237|pmid-6272277|pmid-15809441|NA|pmid-8571451|NA|pmid-16303869|pmid-3293588|pmid-8628994|pmid-4601586|pmid-430569|pmid-9336213|pmid-15783356|pmid-14500788
The property of looping DNA is common to other regulatory proteins and even restriction enzymes
[ "3", "4", "5", "6", "7", "10", "11", "12" ]
95
3,605
0
false
The property of looping DNA is common to other regulatory proteins and even restriction enzymes
[]
The property of looping DNA is common to other regulatory proteins and even restriction enzymes
true
true
false
true
false
601
1
INTRODUCTION
1
3
[ "b3", "b4", "b5", "b6", "b7", "b10", "b11", "b12" ]
16,835,309
pmid-1579106|pmid-4601586|pmid-430569|pmid-10581237|pmid-6272277|pmid-15809441|NA|pmid-8571451|NA|pmid-16303869|pmid-3293588|pmid-8628994|pmid-4601586|pmid-430569|pmid-9336213|pmid-15783356|pmid-14500788
[for a review on DNA looping see (3)].
[ "3", "4", "5", "6", "7", "10", "11", "12" ]
38
3,606
0
false
.
[ "for a review on DNA looping see (3)" ]
.
false
false
true
true
false
601
1
INTRODUCTION
1
3
[ "b3", "b4", "b5", "b6", "b7", "b10", "b11", "b12" ]
16,835,309
pmid-1579106|pmid-4601586|pmid-430569|pmid-10581237|pmid-6272277|pmid-15809441|NA|pmid-8571451|NA|pmid-16303869|pmid-3293588|pmid-8628994|pmid-4601586|pmid-430569|pmid-9336213|pmid-15783356|pmid-14500788
In the Lac operon, the pseudooperators are positioned at 92 and 401 bp from the primary operator (4,5), leading to the possibility of formation of DNA loops of corresponding lengths.
[ "3", "4", "5", "6", "7", "10", "11", "12" ]
182
3,607
0
false
In the Lac operon, the pseudooperators are positioned at 92 and 401 bp from the primary operator, leading to the possibility of formation of DNA loops of corresponding lengths.
[ "4,5" ]
In the Lac operon, the pseudooperators are positioned at 92 and 401 bp from the primary operator, leading to the possibility of formation of DNA loops of corresponding lengths.
true
true
true
true
true
601
1
INTRODUCTION
1
6
[ "b3", "b4", "b5", "b6", "b7", "b10", "b11", "b12" ]
16,835,309
pmid-1579106|pmid-4601586|pmid-430569|pmid-10581237|pmid-6272277|pmid-15809441|NA|pmid-8571451|NA|pmid-16303869|pmid-3293588|pmid-8628994|pmid-4601586|pmid-430569|pmid-9336213|pmid-15783356|pmid-14500788
Depending on the concentration of accessory proteins capable of inducing bends in the DNA molecule and effectively reducing its persistence length (6), the formation of such loops can imply significant bending energies (of the order of several kBT).
[ "3", "4", "5", "6", "7", "10", "11", "12" ]
249
3,608
1
false
Depending on the concentration of accessory proteins capable of inducing bends in the DNA molecule and effectively reducing its persistence length, the formation of such loops can imply significant bending energies (of the order of several kBT).
[ "6" ]
Depending on the concentration of accessory proteins capable of inducing bends in the DNA molecule and effectively reducing its persistence length, the formation of such loops can imply significant bending energies (of the order of several kBT).
true
true
true
true
true
601
1
INTRODUCTION
1
3
[ "b3", "b4", "b5", "b6", "b7", "b10", "b11", "b12" ]
16,835,309
pmid-1579106|pmid-4601586|pmid-430569|pmid-10581237|pmid-6272277|pmid-15809441|NA|pmid-8571451|NA|pmid-16303869|pmid-3293588|pmid-8628994|pmid-4601586|pmid-430569|pmid-9336213|pmid-15783356|pmid-14500788
The effect of the DNA bending energy on the kinetics of protein binding and loop formation, thus represents a potentially important means for the modulation of gene expression regulation at a global or local level on the cell genome.
[ "3", "4", "5", "6", "7", "10", "11", "12" ]
233
3,609
0
false
The effect of the DNA bending energy on the kinetics of protein binding and loop formation, thus represents a potentially important means for the modulation of gene expression regulation at a global or local level on the cell genome.
[]
The effect of the DNA bending energy on the kinetics of protein binding and loop formation, thus represents a potentially important means for the modulation of gene expression regulation at a global or local level on the cell genome.
true
true
true
true
true
601
1
INTRODUCTION
1
3
[ "b3", "b4", "b5", "b6", "b7", "b10", "b11", "b12" ]
16,835,309
pmid-1579106|pmid-4601586|pmid-430569|pmid-10581237|pmid-6272277|pmid-15809441|NA|pmid-8571451|NA|pmid-16303869|pmid-3293588|pmid-8628994|pmid-4601586|pmid-430569|pmid-9336213|pmid-15783356|pmid-14500788
In vitro the role of DNA flexibility on ligase-catalyzed cyclization has been extensively characterized (7–10) and several theoretical studies have been produced to interpret those results (11,12).
[ "3", "4", "5", "6", "7", "10", "11", "12" ]
197
3,610
0
false
In vitro the role of DNA flexibility on ligase-catalyzed cyclization has been extensively characterized and several theoretical studies have been produced to interpret those results.
[ "7–10", "11,12" ]
In vitro the role of DNA flexibility on ligase-catalyzed cyclization has been extensively characterized and several theoretical studies have been produced to interpret those results.
true
true
true
true
true
601
1
INTRODUCTION
1
3
[ "b3", "b4", "b5", "b6", "b7", "b10", "b11", "b12" ]
16,835,309
pmid-1579106|pmid-4601586|pmid-430569|pmid-10581237|pmid-6272277|pmid-15809441|NA|pmid-8571451|NA|pmid-16303869|pmid-3293588|pmid-8628994|pmid-4601586|pmid-430569|pmid-9336213|pmid-15783356|pmid-14500788
From these considerations, a picture is emerging in which DNA is not just simply a passive substrate of regulatory and processing enzymes, but indeed an active player with dynamic physical properties capable of influencing the activity of all DNA-binding proteins.
[ "3", "4", "5", "6", "7", "10", "11", "12" ]
264
3,611
0
false
From these considerations, a picture is emerging in which DNA is not just simply a passive substrate of regulatory and processing enzymes, but indeed an active player with dynamic physical properties capable of influencing the activity of all DNA-binding proteins.
[]
From these considerations, a picture is emerging in which DNA is not just simply a passive substrate of regulatory and processing enzymes, but indeed an active player with dynamic physical properties capable of influencing the activity of all DNA-binding proteins.
true
true
true
true
true
601
1
INTRODUCTION
1
3
[ "b3", "b4", "b5", "b6", "b7", "b10", "b11", "b12" ]
16,835,309
pmid-1579106|pmid-4601586|pmid-430569|pmid-10581237|pmid-6272277|pmid-15809441|NA|pmid-8571451|NA|pmid-16303869|pmid-3293588|pmid-8628994|pmid-4601586|pmid-430569|pmid-9336213|pmid-15783356|pmid-14500788
On the other hand, it is then fundamental to gain understanding of the mechanics of DNA-binding proteins, with particular regard to the interplay between their flexibility and the dependence of their kinetics on the DNA physical properties.
[ "3", "4", "5", "6", "7", "10", "11", "12" ]
240
3,612
0
false
On the other hand, it is then fundamental to gain understanding of the mechanics of DNA-binding proteins, with particular regard to the interplay between their flexibility and the dependence of their kinetics on the DNA physical properties.
[]
On the other hand, it is then fundamental to gain understanding of the mechanics of DNA-binding proteins, with particular regard to the interplay between their flexibility and the dependence of their kinetics on the DNA physical properties.
true
true
true
true
true
601
2
INTRODUCTION
1
13
[ "b13", "b15" ]
16,835,309
pmid-9336213|pmid-15783356|pmid-15630689|pmid-7502073|pmid-10716452|pmid-8139653|pmid-2250707|pmid-8205624|pmid-14500788|pmid-10581237|pmid-16303869|pmid-16361335
Recently, quantitative theories have been formulated on the effects of force on protein–DNA interaction (13–15), leading to the interesting hypothesis that force may play a significant role on gene expression regulation in vivo.
[ "13", "15" ]
228
3,613
0
false
Recently, quantitative theories have been formulated on the effects of force on protein–DNA interaction, leading to the interesting hypothesis that force may play a significant role on gene expression regulation in vivo.
[ "13–15" ]
Recently, quantitative theories have been formulated on the effects of force on protein–DNA interaction, leading to the interesting hypothesis that force may play a significant role on gene expression regulation in vivo.
true
true
true
true
true
602
2
INTRODUCTION
1
13
[ "b13", "b15" ]
16,835,309
pmid-9336213|pmid-15783356|pmid-15630689|pmid-7502073|pmid-10716452|pmid-8139653|pmid-2250707|pmid-8205624|pmid-14500788|pmid-10581237|pmid-16303869|pmid-16361335
Based on these considerations, it is very interesting to investigate the role of DNA and protein mechanics on the mechanism of regulation of gene expression in the Lac operon.
[ "13", "15" ]
175
3,614
0
false
Based on these considerations, it is very interesting to investigate the role of DNA and protein mechanics on the mechanism of regulation of gene expression in the Lac operon.
[]
Based on these considerations, it is very interesting to investigate the role of DNA and protein mechanics on the mechanism of regulation of gene expression in the Lac operon.
true
true
true
true
true
602
3
INTRODUCTION
1
16
[ "b16", "b17", "b18", "b19", "b20" ]
16,835,309
pmid-3301328|pmid-3090685|pmid-8632456|pmid-3667591|pmid-7824935
Direct observation of DNA looping by LacI was first provided by electron microscopy (16).
[ "16", "17", "18", "19", "20" ]
89
3,615
1
false
Direct observation of DNA looping by LacI was first provided by electron microscopy.
[ "16" ]
Direct observation of DNA looping by LacI was first provided by electron microscopy.
true
true
true
true
true
603
3
INTRODUCTION
1
19
[ "b16", "b17", "b18", "b19", "b20" ]
16,835,309
pmid-3301328|pmid-3090685|pmid-8632456|pmid-3667591|pmid-7824935
Measurements in vivo (17,18) and in vitro (19) have provided crucial information on the effects of operators spacing and phasing on the stability of the LacI-induced loop.
[ "16", "17", "18", "19", "20" ]
171
3,616
1
false
Measurements in vivo and in vitro have provided crucial information on the effects of operators spacing and phasing on the stability of the LacI-induced loop.
[ "17,18", "19" ]
Measurements in vivo and in vitro have provided crucial information on the effects of operators spacing and phasing on the stability of the LacI-induced loop.
true
true
true
true
true
603
3
INTRODUCTION
1
16
[ "b16", "b17", "b18", "b19", "b20" ]
16,835,309
pmid-3301328|pmid-3090685|pmid-8632456|pmid-3667591|pmid-7824935
However, a fundamental aspect of repression through DNA looping is represented by the kinetics of formation and disruption of the DNA loop, which are not directly measurable with electron microscopy or biochemical binding assays.
[ "16", "17", "18", "19", "20" ]
229
3,617
0
false
However, a fundamental aspect of repression through DNA looping is represented by the kinetics of formation and disruption of the DNA loop, which are not directly measurable with electron microscopy or biochemical binding assays.
[]
However, a fundamental aspect of repression through DNA looping is represented by the kinetics of formation and disruption of the DNA loop, which are not directly measurable with electron microscopy or biochemical binding assays.
true
true
true
true
true
603
3
INTRODUCTION
1
20
[ "b16", "b17", "b18", "b19", "b20" ]
16,835,309
pmid-3301328|pmid-3090685|pmid-8632456|pmid-3667591|pmid-7824935
With the tethered particle motion (TPM) method, Finzi and Gelles (20) first demonstrated the possibility of observing directly the formation and disruption of a LacI-induced loop in a single DNA molecule and of measuring the kinetics of these processes.
[ "16", "17", "18", "19", "20" ]
253
3,618
1
false
With the tethered particle motion (TPM) method, Finzi and Gelles first demonstrated the possibility of observing directly the formation and disruption of a LacI-induced loop in a single DNA molecule and of measuring the kinetics of these processes.
[ "20" ]
With the tethered particle motion (TPM) method, Finzi and Gelles first demonstrated the possibility of observing directly the formation and disruption of a LacI-induced loop in a single DNA molecule and of measuring the kinetics of these processes.
true
true
true
true
true
603
3
INTRODUCTION
1
16
[ "b16", "b17", "b18", "b19", "b20" ]
16,835,309
pmid-3301328|pmid-3090685|pmid-8632456|pmid-3667591|pmid-7824935
Figure 1 shows a scheme of the TPM system: a DNA molecule containing two appropriately spaced operators is anchored with one end to the surface of a microscope coverslip, while the other end is tagged with a microsphere.
[ "16", "17", "18", "19", "20" ]
220
3,619
0
false
Figure 1 shows a scheme of the TPM system: a DNA molecule containing two appropriately spaced operators is anchored with one end to the surface of a microscope coverslip, while the other end is tagged with a microsphere.
[]
Figure 1 shows a scheme of the TPM system: a DNA molecule containing two appropriately spaced operators is anchored with one end to the surface of a microscope coverslip, while the other end is tagged with a microsphere.
true
true
true
true
true
603
3
INTRODUCTION
1
16
[ "b16", "b17", "b18", "b19", "b20" ]
16,835,309
pmid-3301328|pmid-3090685|pmid-8632456|pmid-3667591|pmid-7824935
The range of Brownian diffusion of the microsphere is limited by the DNA tether.
[ "16", "17", "18", "19", "20" ]
80
3,620
0
false
The range of Brownian diffusion of the microsphere is limited by the DNA tether.
[]
The range of Brownian diffusion of the microsphere is limited by the DNA tether.
true
true
true
true
true
603
3
INTRODUCTION
1
16
[ "b16", "b17", "b18", "b19", "b20" ]
16,835,309
pmid-3301328|pmid-3090685|pmid-8632456|pmid-3667591|pmid-7824935
Upon binding of LacI simultaneously to both operators, the tether is effectively shortened, leading to a measurable reduction in the range of diffusion of the microsphere.
[ "16", "17", "18", "19", "20" ]
171
3,621
0
false
Upon binding of LacI simultaneously to both operators, the tether is effectively shortened, leading to a measurable reduction in the range of diffusion of the microsphere.
[]
Upon binding of LacI simultaneously to both operators, the tether is effectively shortened, leading to a measurable reduction in the range of diffusion of the microsphere.
true
true
true
true
true
603
4
INTRODUCTION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
TPM measurements of a 305 bp long LacI-induced loop indicated that this state is characterized by mono-exponentially distributed durations and does not seem significantly influenced by the bending energy stored in the DNA loop (20).
[ "20" ]
232
3,622
1
false
TPM measurements of a 305 bp long LacI-induced loop indicated that this state is characterized by mono-exponentially distributed durations and does not seem significantly influenced by the bending energy stored in the DNA loop.
[ "20" ]
TPM measurements of a 305 bp long LacI-induced loop indicated that this state is characterized by mono-exponentially distributed durations and does not seem significantly influenced by the bending energy stored in the DNA loop.
true
true
true
true
true
604
4
INTRODUCTION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
The lifetime distribution of the unlooped state, on the other hand, exhibited a more complex shape (at least bi-exponential), as expected of a species which could be due to a manifold of biochemical states (e.g.
[ "20" ]
211
3,623
0
false
The lifetime distribution of the unlooped state, on the other hand, exhibited a more complex shape (at least bi-exponential), as expected of a species which could be due to a manifold of biochemical states (e.g.
[]
The lifetime distribution of the unlooped state, on the other hand, exhibited a more complex shape (at least bi-exponential), as expected of a species which could be due to a manifold of biochemical states (e.g.
true
true
true
true
true
604
4
INTRODUCTION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
both operators vacant, both operators occupied by a LacI tetramer, one operator occupied by LacI tetramer or dimer and the other vacant, and so on).
[ "20" ]
148
3,624
0
false
both operators vacant, both operators occupied by a LacI tetramer, one operator occupied by LacI tetramer or dimer and the other vacant, and so on).
[]
both operators vacant, both operators occupied by a LacI tetramer, one operator occupied by LacI tetramer or dimer and the other vacant, and so on).
false
true
true
true
false
604
4
INTRODUCTION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
Therefore, a more detailed analysis of such distribution (and, thus, of the possible effects of bending and twisting energy on the rate of loop formation) was not attempted.
[ "20" ]
173
3,625
0
false
Therefore, a more detailed analysis of such distribution (and, thus, of the possible effects of bending and twisting energy on the rate of loop formation) was not attempted.
[]
Therefore, a more detailed analysis of such distribution (and, thus, of the possible effects of bending and twisting energy on the rate of loop formation) was not attempted.
true
true
true
true
true
604
5
INTRODUCTION
1
21
[ "b21", "b20" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
In this work we present results obtained applying the TPM technique to the study of wild-type Lac repressor (wt-LacI) at different concentrations, as well as to two mutants of the hinge region: Q60G and Q60 + 1 (21).
[ "21", "20" ]
216
3,626
1
false
In this work we present results obtained applying the TPM technique to the study of wild-type Lac repressor (wt-LacI) at different concentrations, as well as to two mutants of the hinge region: Q60G and Q60 + 1.
[ "21" ]
In this work we present results obtained applying the TPM technique to the study of wild-type Lac repressor (wt-LacI) at different concentrations, as well as to two mutants of the hinge region: Q60G and Q60 + 1.
true
true
true
true
true
605
5
INTRODUCTION
1
21
[ "b21", "b20" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
A full characterization of the TPM data reveals that, due to the limited signal-to-noise ratio of this technique, the measurement of kinetic parameters, such as the average lifetime of the looped and unlooped state, is critically affected by the extent of filtering of the data.
[ "21", "20" ]
278
3,627
0
false
A full characterization of the TPM data reveals that, due to the limited signal-to-noise ratio of this technique, the measurement of kinetic parameters, such as the average lifetime of the looped and unlooped state, is critically affected by the extent of filtering of the data.
[]
A full characterization of the TPM data reveals that, due to the limited signal-to-noise ratio of this technique, the measurement of kinetic parameters, such as the average lifetime of the looped and unlooped state, is critically affected by the extent of filtering of the data.
true
true
true
true
true
605
5
INTRODUCTION
1
21
[ "b21", "b20" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
We elaborated a novel mathematical method for analyzing TPM data and obtained unbiased estimates of the kinetics of looping and unlooping.
[ "21", "20" ]
138
3,628
0
false
We elaborated a novel mathematical method for analyzing TPM data and obtained unbiased estimates of the kinetics of looping and unlooping.
[]
We elaborated a novel mathematical method for analyzing TPM data and obtained unbiased estimates of the kinetics of looping and unlooping.
true
true
true
true
true
605
5
INTRODUCTION
1
21
[ "b21", "b20" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
This provides the basis for obtaining, from this simple single molecule technique, a much more detailed picture of the LacI–DNA interaction mechanisms, including the first experimental evidence for the role of LacI hinge flexibility and DNA bending energy on the kinetics of the process.
[ "21", "20" ]
287
3,629
0
false
This provides the basis for obtaining, from this simple single molecule technique, a much more detailed picture of the LacI–DNA interaction mechanisms, including the first experimental evidence for the role of LacI hinge flexibility and DNA bending energy on the kinetics of the process.
[]
This provides the basis for obtaining, from this simple single molecule technique, a much more detailed picture of the LacI–DNA interaction mechanisms, including the first experimental evidence for the role of LacI hinge flexibility and DNA bending energy on the kinetics of the process.
true
true
true
true
true
605
5
INTRODUCTION
1
20
[ "b21", "b20" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
Using wild-type LacI, we demonstrate that the rate of disruption of the loop is barely affected by the DNA bending energy, as originally suggested also by Finzi and Gelles (20).
[ "21", "20" ]
177
3,630
1
false
Using wild-type LacI, we demonstrate that the rate of disruption of the loop is barely affected by the DNA bending energy, as originally suggested also by Finzi and Gelles.
[ "20" ]
Using wild-type LacI, we demonstrate that the rate of disruption of the loop is barely affected by the DNA bending energy, as originally suggested also by Finzi and Gelles.
true
true
true
true
true
605
5
INTRODUCTION
1
21
[ "b21", "b20" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
On the other hand, our measurements clearly indicate that the rate of formation of the loop is strongly affected by the energetics of DNA bending.
[ "21", "20" ]
146
3,631
0
false
On the other hand, our measurements clearly indicate that the rate of formation of the loop is strongly affected by the energetics of DNA bending.
[]
On the other hand, our measurements clearly indicate that the rate of formation of the loop is strongly affected by the energetics of DNA bending.
true
true
true
true
true
605
5
INTRODUCTION
1
21
[ "b21", "b20" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
To follow up on this well-expected dependence of the rate of loop formation on DNA bending energetics, we investigated also the role of the flexibility of the protein on this process.
[ "21", "20" ]
183
3,632
0
false
To follow up on this well-expected dependence of the rate of loop formation on DNA bending energetics, we investigated also the role of the flexibility of the protein on this process.
[]
To follow up on this well-expected dependence of the rate of loop formation on DNA bending energetics, we investigated also the role of the flexibility of the protein on this process.
true
true
true
true
true
605
5
INTRODUCTION
1
21
[ "b21", "b20" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
Particularly interesting, in this regard, is the flexibility of the hinge region of LacI, which connects the core of the protein with the DNA-binding head.
[ "21", "20" ]
155
3,633
0
false
Particularly interesting, in this regard, is the flexibility of the hinge region of LacI, which connects the core of the protein with the DNA-binding head.
[]
Particularly interesting, in this regard, is the flexibility of the hinge region of LacI, which connects the core of the protein with the DNA-binding head.
true
true
true
true
true
605
5
INTRODUCTION
1
21
[ "b21", "b20" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
The variations of flexibility and geometry of the hinge region in the two mutations studied are associated with very significant changes in the durations of the looped and, to a lesser extent, unlooped states measured by TPM, demonstrating the interplay between DNA and protein flexibility in the modulation of the rates...
[ "21", "20" ]
389
3,634
0
false
The variations of flexibility and geometry of the hinge region in the two mutations studied are associated with very significant changes in the durations of the looped and, to a lesser extent, unlooped states measured by TPM, demonstrating the interplay between DNA and protein flexibility in the modulation of the rates...
[]
The variations of flexibility and geometry of the hinge region in the two mutations studied are associated with very significant changes in the durations of the looped and, to a lesser extent, unlooped states measured by TPM, demonstrating the interplay between DNA and protein flexibility in the modulation of the rates...
true
true
true
true
true
605
5
INTRODUCTION
1
21
[ "b21", "b20" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
Interestingly, the flexibility of the hinge, while drastically changing the looping/unlooping dynamics does not significantly alter the dependence of those dynamics on the DNA strain.
[ "21", "20" ]
183
3,635
0
false
Interestingly, the flexibility of the hinge, while drastically changing the looping/unlooping dynamics does not significantly alter the dependence of those dynamics on the DNA strain.
[]
Interestingly, the flexibility of the hinge, while drastically changing the looping/unlooping dynamics does not significantly alter the dependence of those dynamics on the DNA strain.
true
true
true
true
true
605
6
INTRODUCTION
0
null
null
16,835,309
pmid-16606235|pmid-16606235
These measurements indicate that the Lac operon is a genetic system potentially very sensitive to the mechanics of DNA and of Lac repressor itself.
null
147
3,636
0
false
null
null
These measurements indicate that the Lac operon is a genetic system potentially very sensitive to the mechanics of DNA and of Lac repressor itself.
true
true
true
true
true
606
0
DISCUSSION
1
20
[ "b20", "b24", "b25", "b33", "b36" ]
16,835,309
pmid-13718526|pmid-15950160|pmid-7824935|pmid-13130131|pmid-15155821|pmid-1861724|pmid-16407332
Due to its versatility and simplicity, the TPM method has been used for the study of a variety of biochemical systems at the single molecule level (20,24,25,33–36).
[ "20", "24", "25", "33", "36" ]
164
3,637
0
false
Due to its versatility and simplicity, the TPM method has been used for the study of a variety of biochemical systems at the single molecule level.
[ "20,24,25,33–36" ]
Due to its versatility and simplicity, the TPM method has been used for the study of a variety of biochemical systems at the single molecule level.
true
true
true
true
true
607
0
DISCUSSION
1
20
[ "b20", "b24", "b25", "b33", "b36" ]
16,835,309
pmid-13718526|pmid-15950160|pmid-7824935|pmid-13130131|pmid-15155821|pmid-1861724|pmid-16407332
With regard to dynamic measurements, the main limitation of this experimental approach is represented by the low signal-to-noise ratios that can be accomplished.
[ "20", "24", "25", "33", "36" ]
161
3,638
0
false
With regard to dynamic measurements, the main limitation of this experimental approach is represented by the low signal-to-noise ratios that can be accomplished.
[]
With regard to dynamic measurements, the main limitation of this experimental approach is represented by the low signal-to-noise ratios that can be accomplished.
true
true
true
true
true
607
0
DISCUSSION
1
20
[ "b20", "b24", "b25", "b33", "b36" ]
16,835,309
pmid-13718526|pmid-15950160|pmid-7824935|pmid-13130131|pmid-15155821|pmid-1861724|pmid-16407332
This limitation is mostly determined by the size of the microspheres used, which defines the time necessary for the diffusive motion to explore the volume available for a certain tether length (see Figure 1); variations in the length of the tether can be detected on timescales longer than this characteristic diffusion ...
[ "20", "24", "25", "33", "36" ]
325
3,639
0
false
This limitation is mostly determined by the size of the microspheres used, which defines the time necessary for the diffusive motion to explore the volume available for a certain tether length (see Figure 1); variations in the length of the tether can be detected on timescales longer than this characteristic diffusion ...
[]
This limitation is mostly determined by the size of the microspheres used, which defines the time necessary for the diffusive motion to explore the volume available for a certain tether length (see Figure 1); variations in the length of the tether can be detected on timescales longer than this characteristic diffusion ...
true
true
true
true
true
607
0
DISCUSSION
1
20
[ "b20", "b24", "b25", "b33", "b36" ]
16,835,309
pmid-13718526|pmid-15950160|pmid-7824935|pmid-13130131|pmid-15155821|pmid-1861724|pmid-16407332
This limitation may be overcome and much higher signal-to-noise ratios (or, equivalently, higher temporal resolution in the measurements) may be accomplished substituting much faster diffusing objects (such as quantum dots) for the microspheres thus far used.
[ "20", "24", "25", "33", "36" ]
259
3,640
0
false
This limitation may be overcome and much higher signal-to-noise ratios (or, equivalently, higher temporal resolution in the measurements) may be accomplished substituting much faster diffusing objects (such as quantum dots) for the microspheres thus far used.
[]
This limitation may be overcome and much higher signal-to-noise ratios (or, equivalently, higher temporal resolution in the measurements) may be accomplished substituting much faster diffusing objects (such as quantum dots) for the microspheres thus far used.
true
true
true
true
true
607
0
DISCUSSION
1
20
[ "b20", "b24", "b25", "b33", "b36" ]
16,835,309
pmid-13718526|pmid-15950160|pmid-7824935|pmid-13130131|pmid-15155821|pmid-1861724|pmid-16407332
When implemented using microspheres, however, TPM requires care in the quantitative interpretation of the measured lifetimes.
[ "20", "24", "25", "33", "36" ]
125
3,641
0
false
When implemented using microspheres, however, TPM requires care in the quantitative interpretation of the measured lifetimes.
[]
When implemented using microspheres, however, TPM requires care in the quantitative interpretation of the measured lifetimes.
true
true
true
true
true
607
0
DISCUSSION
1
20
[ "b20", "b24", "b25", "b33", "b36" ]
16,835,309
pmid-13718526|pmid-15950160|pmid-7824935|pmid-13130131|pmid-15155821|pmid-1861724|pmid-16407332
Figure 7, in fact, demonstrates how filtering of the experimental recordings (needed to obtain a good discrimination between the loop and unloop states) strongly influences the values of the measured lifetimes.
[ "20", "24", "25", "33", "36" ]
210
3,642
0
false
Figure 7, in fact, demonstrates how filtering of the experimental recordings (needed to obtain a good discrimination between the loop and unloop states) strongly influences the values of the measured lifetimes.
[]
Figure 7, in fact, demonstrates how filtering of the experimental recordings (needed to obtain a good discrimination between the loop and unloop states) strongly influences the values of the measured lifetimes.
true
true
true
true
true
607
0
DISCUSSION
1
20
[ "b20", "b24", "b25", "b33", "b36" ]
16,835,309
pmid-13718526|pmid-15950160|pmid-7824935|pmid-13130131|pmid-15155821|pmid-1861724|pmid-16407332
We have elaborated a method of analysis of TPM data to overcome these problems and reliably measure the kinetic parameters of Lac repressor-induced loop formation and disruption.
[ "20", "24", "25", "33", "36" ]
178
3,643
0
false
We have elaborated a method of analysis of TPM data to overcome these problems and reliably measure the kinetic parameters of Lac repressor-induced loop formation and disruption.
[]
We have elaborated a method of analysis of TPM data to overcome these problems and reliably measure the kinetic parameters of Lac repressor-induced loop formation and disruption.
true
true
true
true
true
607
1
DISCUSSION
1
37
[ "b37", "b38", "b39", "b40", "b4", "b5", "b13", "b15", "b41" ]
16,835,309
pmid-1579106|pmid-4601586|pmid-430569|pmid-10581237|pmid-6272277|pmid-15809441|NA|pmid-8571451|NA|pmid-16303869|pmid-3293588|pmid-8628994|pmid-4601586|pmid-430569|pmid-9336213|pmid-15783356|pmid-14500788
The formation of the 305 bp long loop in our DNA construct by simultaneous binding of the Lac repressor tetramer to the two operators is associated with a bending energy in the DNA molecule corresponding to about 9.5 kBT (37,38), calculated simplifying the loop geometry to a circle, and with a DNA persistence length of...
[ "37", "38", "39", "40", "4", "5", "13", "15", "41" ]
335
3,644
0
false
The formation of the 305 bp long loop in our DNA construct by simultaneous binding of the Lac repressor tetramer to the two operators is associated with a bending energy in the DNA molecule corresponding to about 9.5 kBT, calculated simplifying the loop geometry to a circle, and with a DNA persistence length of 50 nm.
[ "37,38", "39,40" ]
The formation of the 305 bp long loop in our DNA construct by simultaneous binding of the Lac repressor tetramer to the two operators is associated with a bending energy in the DNA molecule corresponding to about 9.5 kBT, calculated simplifying the loop geometry to a circle, and with a DNA persistence length of 50 nm.
true
true
true
true
true
608
1
DISCUSSION
1
37
[ "b37", "b38", "b39", "b40", "b4", "b5", "b13", "b15", "b41" ]
16,835,309
pmid-1579106|pmid-4601586|pmid-430569|pmid-10581237|pmid-6272277|pmid-15809441|NA|pmid-8571451|NA|pmid-16303869|pmid-3293588|pmid-8628994|pmid-4601586|pmid-430569|pmid-9336213|pmid-15783356|pmid-14500788
The spacing between operators in the Lac operon is 92 and 401 bp (4,5), thus the bending energies involved in the formation of these loops can be significant and may play an important role in the kinetics of transcription regulation.
[ "37", "38", "39", "40", "4", "5", "13", "15", "41" ]
233
3,645
0
false
The spacing between operators in the Lac operon is 92 and 401 bp, thus the bending energies involved in the formation of these loops can be significant and may play an important role in the kinetics of transcription regulation.
[ "4,5" ]
The spacing between operators in the Lac operon is 92 and 401 bp, thus the bending energies involved in the formation of these loops can be significant and may play an important role in the kinetics of transcription regulation.
true
true
true
true
true
608
1
DISCUSSION
1
41
[ "b37", "b38", "b39", "b40", "b4", "b5", "b13", "b15", "b41" ]
16,835,309
pmid-1579106|pmid-4601586|pmid-430569|pmid-10581237|pmid-6272277|pmid-15809441|NA|pmid-8571451|NA|pmid-16303869|pmid-3293588|pmid-8628994|pmid-4601586|pmid-430569|pmid-9336213|pmid-15783356|pmid-14500788
The effects of DNA tension and torsion on the kinetics of DNA-binding proteins have recently been explored in a variety of theoretical studies (13–15) and in experimental measurements on Gal repressor (41).
[ "37", "38", "39", "40", "4", "5", "13", "15", "41" ]
206
3,646
1
false
The effects of DNA tension and torsion on the kinetics of DNA-binding proteins have recently been explored in a variety of theoretical studies and in experimental measurements on Gal repressor.
[ "13–15", "41" ]
The effects of DNA tension and torsion on the kinetics of DNA-binding proteins have recently been explored in a variety of theoretical studies and in experimental measurements on Gal repressor.
true
true
true
true
true
608
2
DISCUSSION
1
42
[ "b42", "b43", "b45", "b46", "b47", "b48", "b41", "b6", "b38", "b49" ]
16,835,309
pmid-9336213|pmid-15783356|pmid-15630689|pmid-7502073|pmid-10716452|pmid-8139653|pmid-2250707|pmid-8205624|pmid-14500788|pmid-10581237|pmid-16303869|pmid-16361335
Single molecule approaches are providing fundamental information on the mechanical properties of a growing number of enzymatic systems in vitro (42).
[ "42", "43", "45", "46", "47", "48", "41", "6", "38", "49" ]
149
3,647
1
false
Single molecule approaches are providing fundamental information on the mechanical properties of a growing number of enzymatic systems in vitro.
[ "42" ]
Single molecule approaches are providing fundamental information on the mechanical properties of a growing number of enzymatic systems in vitro.
true
true
true
true
true
609
2
DISCUSSION
1
46
[ "b42", "b43", "b45", "b46", "b47", "b48", "b41", "b6", "b38", "b49" ]
16,835,309
pmid-9336213|pmid-15783356|pmid-15630689|pmid-7502073|pmid-10716452|pmid-8139653|pmid-2250707|pmid-8205624|pmid-14500788|pmid-10581237|pmid-16303869|pmid-16361335
The measurement of forces in the pN range has indicated nucleic acid processing enzymes (such as RNA polymerase, DNA polymerase, topoisomerases) as molecular motors (43–45) capable of producing forces even larger than those of ‘classic’ motors, such as myosin (46) or kinesin (47,48).
[ "42", "43", "45", "46", "47", "48", "41", "6", "38", "49" ]
284
3,648
1
false
The measurement of forces in the pN range has indicated nucleic acid processing enzymes (such as RNA polymerase, DNA polymerase, topoisomerases) as molecular motors capable of producing forces even larger than those of ‘classic’ motors, such as myosin or kinesin.
[ "43–45", "46", "47,48" ]
The measurement of forces in the pN range has indicated nucleic acid processing enzymes (such as RNA polymerase, DNA polymerase, topoisomerases) as molecular motors capable of producing forces even larger than those of ‘classic’ motors, such as myosin or kinesin.
true
true
true
true
true
609
2
DISCUSSION
1
42
[ "b42", "b43", "b45", "b46", "b47", "b48", "b41", "b6", "b38", "b49" ]
16,835,309
pmid-9336213|pmid-15783356|pmid-15630689|pmid-7502073|pmid-10716452|pmid-8139653|pmid-2250707|pmid-8205624|pmid-14500788|pmid-10581237|pmid-16303869|pmid-16361335
These forces may be crucial for these enzymes to overcome obstacles, unwind double-stranded structures and move along the DNA template under the conditions of compaction, tension and torsion to which it is subject in vivo.
[ "42", "43", "45", "46", "47", "48", "41", "6", "38", "49" ]
222
3,649
0
false
These forces may be crucial for these enzymes to overcome obstacles, unwind double-stranded structures and move along the DNA template under the conditions of compaction, tension and torsion to which it is subject in vivo.
[]
These forces may be crucial for these enzymes to overcome obstacles, unwind double-stranded structures and move along the DNA template under the conditions of compaction, tension and torsion to which it is subject in vivo.
true
true
true
true
true
609
2
DISCUSSION
1
42
[ "b42", "b43", "b45", "b46", "b47", "b48", "b41", "b6", "b38", "b49" ]
16,835,309
pmid-9336213|pmid-15783356|pmid-15630689|pmid-7502073|pmid-10716452|pmid-8139653|pmid-2250707|pmid-8205624|pmid-14500788|pmid-10581237|pmid-16303869|pmid-16361335
Transcription regulation systems, including the Lac operon, are sensitive to these forces to the extent by which binding and dissociation of the regulatory proteins are influenced by the bending and twisting energetics of the DNA.
[ "42", "43", "45", "46", "47", "48", "41", "6", "38", "49" ]
230
3,650
0
false
Transcription regulation systems, including the Lac operon, are sensitive to these forces to the extent by which binding and dissociation of the regulatory proteins are influenced by the bending and twisting energetics of the DNA.
[]
Transcription regulation systems, including the Lac operon, are sensitive to these forces to the extent by which binding and dissociation of the regulatory proteins are influenced by the bending and twisting energetics of the DNA.
true
true
true
true
true
609
2
DISCUSSION
1
41
[ "b42", "b43", "b45", "b46", "b47", "b48", "b41", "b6", "b38", "b49" ]
16,835,309
pmid-9336213|pmid-15783356|pmid-15630689|pmid-7502073|pmid-10716452|pmid-8139653|pmid-2250707|pmid-8205624|pmid-14500788|pmid-10581237|pmid-16303869|pmid-16361335
Measurements based on the use of magnetic tweezers have clearly demonstrated the sensitivity of the GalR system to supercoiling in the DNA target molecule (41).
[ "42", "43", "45", "46", "47", "48", "41", "6", "38", "49" ]
160
3,651
1
false
Measurements based on the use of magnetic tweezers have clearly demonstrated the sensitivity of the GalR system to supercoiling in the DNA target molecule.
[ "41" ]
Measurements based on the use of magnetic tweezers have clearly demonstrated the sensitivity of the GalR system to supercoiling in the DNA target molecule.
true
true
true
true
true
609
2
DISCUSSION
1
6
[ "b42", "b43", "b45", "b46", "b47", "b48", "b41", "b6", "b38", "b49" ]
16,835,309
pmid-9336213|pmid-15783356|pmid-15630689|pmid-7502073|pmid-10716452|pmid-8139653|pmid-2250707|pmid-8205624|pmid-14500788|pmid-10581237|pmid-16303869|pmid-16361335
The persistence length of DNA in vivo is much lower than that measured in vitro (6), due to the action of accessory proteins.
[ "42", "43", "45", "46", "47", "48", "41", "6", "38", "49" ]
125
3,652
1
false
The persistence length of DNA in vivo is much lower than that measured in vitro, due to the action of accessory proteins.
[ "6" ]
The persistence length of DNA in vivo is much lower than that measured in vitro, due to the action of accessory proteins.
true
true
true
true
true
609
2
DISCUSSION
1
42
[ "b42", "b43", "b45", "b46", "b47", "b48", "b41", "b6", "b38", "b49" ]
16,835,309
pmid-9336213|pmid-15783356|pmid-15630689|pmid-7502073|pmid-10716452|pmid-8139653|pmid-2250707|pmid-8205624|pmid-14500788|pmid-10581237|pmid-16303869|pmid-16361335
It is presumable that this physical property of DNA can be modulated to some extent by the quantity and quality of accessory proteins expressed in the cell.
[ "42", "43", "45", "46", "47", "48", "41", "6", "38", "49" ]
156
3,653
0
false
It is presumable that this physical property of DNA can be modulated to some extent by the quantity and quality of accessory proteins expressed in the cell.
[]
It is presumable that this physical property of DNA can be modulated to some extent by the quantity and quality of accessory proteins expressed in the cell.
true
true
true
true
true
609
2
DISCUSSION
1
42
[ "b42", "b43", "b45", "b46", "b47", "b48", "b41", "b6", "b38", "b49" ]
16,835,309
pmid-9336213|pmid-15783356|pmid-15630689|pmid-7502073|pmid-10716452|pmid-8139653|pmid-2250707|pmid-8205624|pmid-14500788|pmid-10581237|pmid-16303869|pmid-16361335
Thus, a new concept is recently emerging in gene regulation: the physical properties of DNA may play an important role in shaping the dynamics of gene regulation (38,49).
[ "42", "43", "45", "46", "47", "48", "41", "6", "38", "49" ]
170
3,654
0
false
Thus, a new concept is recently emerging in gene regulation: the physical properties of DNA may play an important role in shaping the dynamics of gene regulation.
[ "38,49" ]
Thus, a new concept is recently emerging in gene regulation: the physical properties of DNA may play an important role in shaping the dynamics of gene regulation.
true
true
true
true
true
609
3
DISCUSSION
0
null
null
16,835,309
pmid-3301328|pmid-3090685|pmid-8632456|pmid-3667591|pmid-7824935
We have applied the TPM technique, in combination with a new method for data analysis, to the investigation of the effects of flexibility (both in DNA and in the hinge region of the protein) on the kinetics of loop formation and disruption.
null
240
3,655
0
false
null
null
We have applied the TPM technique, in combination with a new method for data analysis, to the investigation of the effects of flexibility (both in DNA and in the hinge region of the protein) on the kinetics of loop formation and disruption.
true
true
true
true
true
610
4
DISCUSSION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
The analysis of the kinetics of loop disruption is simplified by the fact that there is a 1:1 correspondence between the TPM state of lower microsphere mobility and the biochemical ORO state (see Figure 6).
[ "20" ]
206
3,656
0
false
The analysis of the kinetics of loop disruption is simplified by the fact that there is a 1:1 correspondence between the TPM state of lower microsphere mobility and the biochemical ORO state (see Figure 6).
[]
The analysis of the kinetics of loop disruption is simplified by the fact that there is a 1:1 correspondence between the TPM state of lower microsphere mobility and the biochemical ORO state (see Figure 6).
true
true
true
true
true
611
4
DISCUSSION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
This correspondence is confirmed by the lack of dependence of τLm on LacI concentration (Figure 4, left panels; Figure 7a, filled symbols).
[ "20" ]
139
3,657
0
false
This correspondence is confirmed by the lack of dependence of τLm on LacI concentration (Figure 4, left panels; Figure 7a, filled symbols).
[]
This correspondence is confirmed by the lack of dependence of τLm on LacI concentration (Figure 4, left panels; Figure 7a, filled symbols).
true
true
true
true
true
611
4
DISCUSSION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
In fact, as an alternative interpretation, one could imagine a fast equilibrium between O-OR and ORO, characterized by rates much faster then the diffusion rate of the microsphere and shifted toward ORO, so to give raise to an apparent TPM loop state concealing fast biochemical reactions.
[ "20" ]
289
3,658
0
false
In fact, as an alternative interpretation, one could imagine a fast equilibrium between O-OR and ORO, characterized by rates much faster then the diffusion rate of the microsphere and shifted toward ORO, so to give raise to an apparent TPM loop state concealing fast biochemical reactions.
[]
In fact, as an alternative interpretation, one could imagine a fast equilibrium between O-OR and ORO, characterized by rates much faster then the diffusion rate of the microsphere and shifted toward ORO, so to give raise to an apparent TPM loop state concealing fast biochemical reactions.
true
true
true
true
true
611
4
DISCUSSION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
However, if this were the case, one would expect the durations of the observed TPM loop state to depend on the concentration of LacI.
[ "20" ]
133
3,659
0
false
However, if this were the case, one would expect the durations of the observed TPM loop state to depend on the concentration of LacI.
[]
However, if this were the case, one would expect the durations of the observed TPM loop state to depend on the concentration of LacI.
true
true
true
true
true
611
4
DISCUSSION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
In fact, the exit from the fast equilibrium would be determined by a reaction leading the system into a third, long lived, state.
[ "20" ]
129
3,660
0
false
In fact, the exit from the fast equilibrium would be determined by a reaction leading the system into a third, long lived, state.
[]
In fact, the exit from the fast equilibrium would be determined by a reaction leading the system into a third, long lived, state.
true
true
true
true
true
611
4
DISCUSSION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
The most relevant long lived state in this regard depends on the concentration of LacI, and thus the entire behavior of the system is dependent on this parameter.
[ "20" ]
162
3,661
0
false
The most relevant long lived state in this regard depends on the concentration of LacI, and thus the entire behavior of the system is dependent on this parameter.
[]
The most relevant long lived state in this regard depends on the concentration of LacI, and thus the entire behavior of the system is dependent on this parameter.
true
true
true
true
true
611
4
DISCUSSION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
More precisely, the ratio between the rates from O-OR toward RO-OR and O-O is given by [LacI]/KD, which has a value of about 10, 2 and 0.4 for [LacI] of 100, 20 and 4 pM, respectively.
[ "20" ]
184
3,662
0
false
More precisely, the ratio between the rates from O-OR toward RO-OR and O-O is given by [LacI]/KD, which has a value of about 10, 2 and 0.4 for [LacI] of 100, 20 and 4 pM, respectively.
[]
More precisely, the ratio between the rates from O-OR toward RO-OR and O-O is given by [LacI]/KD, which has a value of about 10, 2 and 0.4 for [LacI] of 100, 20 and 4 pM, respectively.
true
true
true
true
true
611
4
DISCUSSION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
At the two higher concentrations, RO-OR is, thus, prevalent: under these conditions, the rate of transition between O-OR and the other main unloop state scales linearly with [LacI].
[ "20" ]
181
3,663
0
false
At the two higher concentrations, RO-OR is, thus, prevalent: under these conditions, the rate of transition between O-OR and the other main unloop state scales linearly with [LacI].
[]
At the two higher concentrations, RO-OR is, thus, prevalent: under these conditions, the rate of transition between O-OR and the other main unloop state scales linearly with [LacI].
true
true
true
true
true
611
4
DISCUSSION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
Thus, the probability of exiting the above mentioned hypothetical equilibrium would also scale linearly with [LacI].
[ "20" ]
116
3,664
0
false
Thus, the probability of exiting the above mentioned hypothetical equilibrium would also scale linearly with [LacI].
[]
Thus, the probability of exiting the above mentioned hypothetical equilibrium would also scale linearly with [LacI].
true
true
true
true
true
611
4
DISCUSSION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
Since the measured duration of the TPM loop state does not depend on the concentration of LacI over a broad range of concentrations [4, 20 and 100 pM tested in this work, and 100 pM and 1 nM tested by Finzi and Gelles (20)]
[ "20" ]
223
3,665
0
false
Since the measured duration of the TPM loop state does not depend on the concentration of LacI over a broad range of concentrations
[ "4, 20 and 100 pM tested in this work, and 100 pM and 1 nM tested by Finzi and Gelles (20)" ]
Since the measured duration of the TPM loop state does not depend on the concentration of LacI over a broad range of concentrations
true
true
false
true
false
611
4
DISCUSSION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
the hypothesis of the TPM loop state underlying a fast biochemical equilibrium is not likely; rather, the exit from this TPM state monitors directly the disruption of the loop in the DNA molecule.
[ "20" ]
196
3,666
0
false
the hypothesis of the TPM loop state underlying a fast biochemical equilibrium is not likely; rather, the exit from this TPM state monitors directly the disruption of the loop in the DNA molecule.
[]
the hypothesis of the TPM loop state underlying a fast biochemical equilibrium is not likely; rather, the exit from this TPM state monitors directly the disruption of the loop in the DNA molecule.
false
true
true
true
false
611
4
DISCUSSION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
Thus, the TPM measurement provides a means for directly monitoring the effect of the loop strain on the kinetics of dissociation, as described in the results by the parameter α.
[ "20" ]
177
3,667
0
false
Thus, the TPM measurement provides a means for directly monitoring the effect of the loop strain on the kinetics of dissociation, as described in the results by the parameter α.
[]
Thus, the TPM measurement provides a means for directly monitoring the effect of the loop strain on the kinetics of dissociation, as described in the results by the parameter α.
true
true
true
true
true
611
4
DISCUSSION
1
20
[ "b20" ]
16,835,309
pmid-7824935|pmid-7824935
Our findings indicate a weak dependence of the rate of loop disruption on the DNA bending and twisting energy, as demonstrated by the value of α between 1 and 2.
[ "20" ]
161
3,668
0
false
Our findings indicate a weak dependence of the rate of loop disruption on the DNA bending and twisting energy, as demonstrated by the value of α between 1 and 2.
[]
Our findings indicate a weak dependence of the rate of loop disruption on the DNA bending and twisting energy, as demonstrated by the value of α between 1 and 2.
true
true
true
true
true
611
5
DISCUSSION
1
8
[ "b8", "b11" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
With regard to the kinetics of loop formation, on the other hand, our measurements indicate that formation of a loop in the DNA molecule by binding of Lac repressor simultaneously to two operators is highly sensitive to the DNA bending energy.
[ "8", "11" ]
243
3,669
0
false
With regard to the kinetics of loop formation, on the other hand, our measurements indicate that formation of a loop in the DNA molecule by binding of Lac repressor simultaneously to two operators is highly sensitive to the DNA bending energy.
[]
With regard to the kinetics of loop formation, on the other hand, our measurements indicate that formation of a loop in the DNA molecule by binding of Lac repressor simultaneously to two operators is highly sensitive to the DNA bending energy.
true
true
true
true
true
612
5
DISCUSSION
1
8
[ "b8", "b11" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
Qualitatively, this result is well-expected based both on theoretical considerations and previous ligase-catalyzed circularization experiments; however, our results on LacI are somewhat surprising quantitatively.
[ "8", "11" ]
212
3,670
0
false
Qualitatively, this result is well-expected based both on theoretical considerations and previous ligase-catalyzed circularization experiments; however, our results on LacI are somewhat surprising quantitatively.
[]
Qualitatively, this result is well-expected based both on theoretical considerations and previous ligase-catalyzed circularization experiments; however, our results on LacI are somewhat surprising quantitatively.
true
true
true
true
true
612
5
DISCUSSION
1
11
[ "b8", "b11" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
In fact, the values we have obtained for Jm (of the order of 10−10 M) are significantly lower than those measured by ligase-catalyzed cyclization experiments [>10−8 M for DNA segments of 300 bp (8)] and calculated from physical models of the DNA molecule (11).
[ "8", "11" ]
260
3,671
1
false
In fact, the values we have obtained for Jm (of the order of 10−10 M) are significantly lower than those measured by ligase-catalyzed cyclization experiments and calculated from physical models of the DNA molecule.
[ ">10−8 M for DNA segments of 300 bp (8)", "11" ]
In fact, the values we have obtained for Jm are significantly lower than those measured by ligase-catalyzed cyclization experiments and calculated from physical models of the DNA molecule.
true
true
true
true
true
612
5
DISCUSSION
1
8
[ "b8", "b11" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
It is fundamental to evaluate the effects of the microsphere on the values measured for Jm by TPM technique.
[ "8", "11" ]
108
3,672
0
false
It is fundamental to evaluate the effects of the microsphere on the values measured for Jm by TPM technique.
[]
It is fundamental to evaluate the effects of the microsphere on the values measured for Jm by TPM technique.
true
true
true
true
true
612
5
DISCUSSION
1
8
[ "b8", "b11" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
It is expected, in fact, that the presence of the microsphere may slow down the kinetics of loop formation, due to an effective swelling force exerted entropically by the microsphere on the polymer.
[ "8", "11" ]
198
3,673
0
false
It is expected, in fact, that the presence of the microsphere may slow down the kinetics of loop formation, due to an effective swelling force exerted entropically by the microsphere on the polymer.
[]
It is expected, in fact, that the presence of the microsphere may slow down the kinetics of loop formation, due to an effective swelling force exerted entropically by the microsphere on the polymer.
true
true
true
true
true
612
5
DISCUSSION
1
8
[ "b8", "b11" ]
16,835,309
pmid-10521477|pmid-7824935|pmid-6315955|NA
Below we will discuss results indicating that, in a system like the one we setup for the measurements on LacI, the effect of the microsphere on the measured kinetics of loop formation (and, therefore, on the measured Jm) should not exceed, at most, a factor of 10.
[ "8", "11" ]
264
3,674
0
false
Below we will discuss results indicating that, in a system like the one we setup for the measurements on LacI, the effect of the microsphere on the measured kinetics of loop formation (and, therefore, on the measured Jm) should not exceed, at most, a factor of 10.
[]
Below we will discuss results indicating that, in a system like the one we setup for the measurements on LacI, the effect of the microsphere on the measured kinetics of loop formation (and, therefore, on the measured Jm) should not exceed, at most, a factor of 10.
true
true
true
true
true
612
6
DISCUSSION
1
50
[ "b50", "b50" ]
16,835,309
pmid-16606235|pmid-16606235
In their theoretical work, extensively modeling the physical properties of the TPM system, Segall et al.
[ "50", "50" ]
104
3,675
0
false
In their theoretical work, extensively modeling the physical properties of the TPM system, Segall et al.
[]
In their theoretical work, extensively modeling the physical properties of the TPM system, Segall et al.
true
true
true
true
true
613
6
DISCUSSION
1
50
[ "b50", "b50" ]
16,835,309
pmid-16606235|pmid-16606235
provide an analytical expression [Equation 12 in Ref.
[ "50", "50" ]
53
3,676
0
false
provide an analytical expression [Equation 12 in Ref.
[]
provide an analytical expression [Equation 12 in Ref.
false
true
true
true
false
613
6
DISCUSSION
1
50
[ "b50", "b50" ]
16,835,309
pmid-16606235|pmid-16606235
(50)] for the swelling force as a function of DNA contour length, persistence length and microsphere radius.
[ "50", "50" ]
108
3,677
1
false
] for the swelling force as a function of DNA contour length, persistence length and microsphere radius.
[ "50" ]
] for the swelling force as a function of DNA contour length, persistence length and microsphere radius.
false
false
true
true
false
613
6
DISCUSSION
1
50
[ "b50", "b50" ]
16,835,309
pmid-16606235|pmid-16606235
In our experimental system, the swelling force estimated according to this expression is about 30 fN.
[ "50", "50" ]
101
3,678
0
false
In our experimental system, the swelling force estimated according to this expression is about 30 fN.
[]
In our experimental system, the swelling force estimated according to this expression is about 30 fN.
true
true
true
true
true
613
6
DISCUSSION
1
50
[ "b50", "b50" ]
16,835,309
pmid-16606235|pmid-16606235
Segall et al.
[ "50", "50" ]
13
3,679
0
false
Segall et al.
[]
Segall et al.
true
true
true
true
true
613
6
DISCUSSION
1
50
[ "b50", "b50" ]
16,835,309
pmid-16606235|pmid-16606235
(50) conclude that a force of this magnitude due to the presence of the microsphere would decrease the rate of looping by about a factor of 2.
[ "50", "50" ]
142
3,680
1
false
conclude that a force of this magnitude due to the presence of the microsphere would decrease the rate of looping by about a factor of 2.
[ "50" ]
conclude that a force of this magnitude due to the presence of the microsphere would decrease the rate of looping by about a factor of 2.
false
true
true
true
false
613
7
DISCUSSION
1
25
[ "b25", "b50", "b14", "b51" ]
16,835,309
pmid-15155821|pmid-16606235|pmid-15653717|pmid-16089763
Further, the TPM recordings of the position distributions of the microsphere in the absence of Lac repressor exhibit interesting non-Gaussian features (25) which may be exploited to estimate the magnitude of the swelling force.
[ "25", "50", "14", "51" ]
227
3,681
1
false
Further, the TPM recordings of the position distributions of the microsphere in the absence of Lac repressor exhibit interesting non-Gaussian features which may be exploited to estimate the magnitude of the swelling force.
[ "25" ]
Further, the TPM recordings of the position distributions of the microsphere in the absence of Lac repressor exhibit interesting non-Gaussian features which may be exploited to estimate the magnitude of the swelling force.
true
true
true
true
true
614
7
DISCUSSION
1
25
[ "b25", "b50", "b14", "b51" ]
16,835,309
pmid-15155821|pmid-16606235|pmid-15653717|pmid-16089763
Using numerical simulations of the TPM system [similar to those described by Segall et al.
[ "25", "50", "14", "51" ]
90
3,682
0
false
Using numerical simulations of the TPM system [similar to those described by Segall et al.
[]
Using numerical simulations of the TPM system [similar to those described by Segall et al.
true
true
true
true
true
614
7
DISCUSSION
1
50
[ "b25", "b50", "b14", "b51" ]
16,835,309
pmid-15155821|pmid-16606235|pmid-15653717|pmid-16089763
(50)] to fit our data, we have estimated in our system an effective swelling force of 127 ± 14 fN (best estimate ± range for 95.4% confidence; see Supplementary Data).
[ "25", "50", "14", "51" ]
167
3,683
1
false
] to fit our data, we have estimated in our system an effective swelling force of 127 ± 14 fN (best estimate ± range for 95.4% confidence; see Supplementary Data).
[ "50" ]
] to fit our data, we have estimated in our system an effective swelling force of 127 ± 14 fN.
false
false
true
true
false
614
7
DISCUSSION
1
25
[ "b25", "b50", "b14", "b51" ]
16,835,309
pmid-15155821|pmid-16606235|pmid-15653717|pmid-16089763
Recent theoretical works (14,51) have described the effects of force on Jm: a force in the range between 30 and 140 fN due to the presence of the microsphere would not be expected to decrease Jm by more than a factor of 10.
[ "25", "50", "14", "51" ]
223
3,684
0
false
Recent theoretical works have described the effects of force on Jm: a force in the range between 30 and 140 fN due to the presence of the microsphere would not be expected to decrease Jm by more than a factor of 10.
[ "14,51" ]
Recent theoretical works have described the effects of force on Jm: a force in the range between 30 and 140 fN due to the presence of the microsphere would not be expected to decrease Jm by more than a factor of 10.
true
true
true
true
true
614
8
DISCUSSION
1
19
[ "b19", "b50" ]
16,835,309
pmid-3667591|pmid-16606235
Finally, Hsieh et al.
[ "19", "50" ]
21
3,685
0
false
Finally, Hsieh et al.
[]
Finally, Hsieh et al.
true
true
true
true
true
615
8
DISCUSSION
1
19
[ "b19", "b50" ]
16,835,309
pmid-3667591|pmid-16606235
(19) reported an estimate of the equilibrium constant K* for the intramolecular looping reaction: for the pRW490 construct containing the two primary operators at a distance of 305 bp from each other, they reported a value of 16 for K*.
[ "19", "50" ]
236
3,686
1
false
reported an estimate of the equilibrium constant K* for the intramolecular looping reaction: for the pRW490 construct containing the two primary operators at a distance of 305 bp from each other, they reported a value of 16 for K*.
[ "19" ]
reported an estimate of the equilibrium constant K* for the intramolecular looping reaction: for the pRW490 construct containing the two primary operators at a distance of 305 bp from each other, they reported a value of 16 for K*.
false
true
true
true
false
615
8
DISCUSSION
1
19
[ "b19", "b50" ]
16,835,309
pmid-3667591|pmid-16606235
In our measurements, the equilibrium constant for the intramolecular looping reaction is given by K′ = Jmka / (2kdα).
[ "19", "50" ]
117
3,687
0
false
In our measurements, the equilibrium constant for the intramolecular looping reaction is given by K′ = Jmka / (2kdα).
[]
In our measurements, the equilibrium constant for the intramolecular looping reaction is given by K′ = Jmka / (2kdα).
true
true
true
true
true
615
8
DISCUSSION
1
19
[ "b19", "b50" ]
16,835,309
pmid-3667591|pmid-16606235
Using the values of Jm and α reported in Table 1 we obtain K′ between 2.5 and 7.
[ "19", "50" ]
80
3,688
0
false
Using the values of Jm and α reported in Table 1 we obtain K′ between 2.5 and 7.
[]
Using the values of Jm and α reported in Table 1 we obtain K′ between 2.5 and 7.
true
true
true
true
true
615
8
DISCUSSION
1
19
[ "b19", "b50" ]
16,835,309
pmid-3667591|pmid-16606235
The difference between K* and K′ is to be attributed to the microsphere, according to the following relationship: −RT ln(K′) =
[ "19", "50" ]
126
3,689
0
false
The difference between K* and K′ is to be attributed to the microsphere, according to the following relationship: −RT ln(K′) =
[]
The difference between K* and K′ is to be attributed to the microsphere, according to the following relationship: −RT ln(K′) =
true
true
false
true
false
615
8
DISCUSSION
1
19
[ "b19", "b50" ]
16,835,309
pmid-3667591|pmid-16606235
ΔGtpm = ΔGDNA/LacI +
[ "19", "50" ]
20
3,690
0
false
ΔGtpm = ΔGDNA/LacI +
[]
ΔGtpm = ΔGDNA/LacI +
true
true
false
true
false
615
8
DISCUSSION
1
19
[ "b19", "b50" ]
16,835,309
pmid-3667591|pmid-16606235
ΔGbead, where ΔGDNA/LacI =
[ "19", "50" ]
26
3,691
0
false
ΔGbead, where ΔGDNA/LacI =
[]
ΔGbead, where ΔGDNA/LacI =
true
true
false
true
false
615
8
DISCUSSION
1
19
[ "b19", "b50" ]
16,835,309
pmid-3667591|pmid-16606235
−RT ln(K*) is the free energy of looping in the absence of microsphere and ΔGbead is the positive free energy contribution due to the microsphere opposing an entropic force to the formation of the loop.
[ "19", "50" ]
202
3,692
0
false
−RT ln(K*) is the free energy of looping in the absence of microsphere and ΔGbead is the positive free energy contribution due to the microsphere opposing an entropic force to the formation of the loop.
[]
−RT ln(K*) is the free energy of looping in the absence of microsphere and ΔGbead is the positive free energy contribution due to the microsphere opposing an entropic force to the formation of the loop.
false
false
true
true
false
615
8
DISCUSSION
1
19
[ "b19", "b50" ]
16,835,309
pmid-3667591|pmid-16606235
From these relations, based on the measurement of K′ reported above, we estimate ΔGbead between 0.8 and 1.8 kBT.
[ "19", "50" ]
112
3,693
0
false
From these relations, based on the measurement of K′ reported above, we estimate ΔGbead between 0.8 and 1.8 kBT.
[]
From these relations, based on the measurement of K′ reported above, we estimate ΔGbead between 0.8 and 1.8 kBT.
true
true
true
true
true
615
8
DISCUSSION
1
19
[ "b19", "b50" ]
16,835,309
pmid-3667591|pmid-16606235
If we assume that this energetic barrier affects mostly the rate of formation of the loop, this would lead to a reduction of the looping rate by at most 55–83%, in agreement with what calculated by Segall et al.
[ "19", "50" ]
211
3,694
0
false
If we assume that this energetic barrier affects mostly the rate of formation of the loop, this would lead to a reduction of the looping rate by at most 55–83%, in agreement with what calculated by Segall et al.
[]
If we assume that this energetic barrier affects mostly the rate of formation of the loop, this would lead to a reduction of the looping rate by at most 55–83%, in agreement with what calculated by Segall et al.
true
true
true
true
true
615
8
DISCUSSION
1
19
[ "b19", "b50" ]
16,835,309
pmid-3667591|pmid-16606235
Thus, we conclude that, even accounting for an underestimation of Jm by about an order of magnitude in TPM due to the microsphere, Lac repressor looping is characterized by a Jm much (at least 10 times) lower than the ligase-catalyzed circularization of a DNA segment of the same length.
[ "19", "50" ]
287
3,695
0
false
Thus, we conclude that, even accounting for an underestimation of Jm by about an order of magnitude in TPM due to the microsphere, Lac repressor looping is characterized by a Jm much (at least 10 times) lower than the ligase-catalyzed circularization of a DNA segment of the same length.
[]
Thus, we conclude that, even accounting for an underestimation of Jm by about an order of magnitude in TPM due to the microsphere, Lac repressor looping is characterized by a Jm much lower than the ligase-catalyzed circularization of a DNA segment of the same length.
true
true
true
true
true
615
9
DISCUSSION
1
15
[ "b15", "b49", "b52", "b53" ]
16,835,309
pmid-15783356|pmid-16361335|pmid-9533690|pmid-11738597
The shape of a DNA loop can vary over a wide range of geometries determining large variations in the loop energetics and in the resulting Jm values (15,49), with significant deviations from those measured in cyclization experiments.
[ "15", "49", "52", "53" ]
232
3,696
0
false
The shape of a DNA loop can vary over a wide range of geometries determining large variations in the loop energetics and in the resulting Jm values, with significant deviations from those measured in cyclization experiments.
[ "15,49" ]
The shape of a DNA loop can vary over a wide range of geometries determining large variations in the loop energetics and in the resulting Jm values, with significant deviations from those measured in cyclization experiments.
true
true
true
true
true
616
9
DISCUSSION
1
15
[ "b15", "b49", "b52", "b53" ]
16,835,309
pmid-15783356|pmid-16361335|pmid-9533690|pmid-11738597
Also, the effect of the protein bridging between the two extremities of the loop significantly influences the calculated values of Jm (52,53).
[ "15", "49", "52", "53" ]
142
3,697
0
false
Also, the effect of the protein bridging between the two extremities of the loop significantly influences the calculated values of Jm.
[ "52,53" ]
Also, the effect of the protein bridging between the two extremities of the loop significantly influences the calculated values of Jm.
true
true
true
true
true
616
10
DISCUSSION
1
54
[ "b54", "b55" ]
16,835,309
pmid-8638105|pmid-12547794
The structure of the DNA–LacI complex in the looped configuration has not yet been determined.
[ "54", "55" ]
94
3,698
0
false
The structure of the DNA–LacI complex in the looped configuration has not yet been determined.
[]
The structure of the DNA–LacI complex in the looped configuration has not yet been determined.
true
true
true
true
true
617
10
DISCUSSION
1
54
[ "b54", "b55" ]
16,835,309
pmid-8638105|pmid-12547794
In addition to the original V-shaped model, proposed by Lewis et al.
[ "54", "55" ]
68
3,699
0
false
In addition to the original V-shaped model, proposed by Lewis et al.
[]
In addition to the original V-shaped model, proposed by Lewis et al.
true
true
true
true
true
617