All motors have to decide is what to do with the DNA that is given them

Briggs, Koan; Fischer, Christopher J.

doi:10.1515/bmc-2014-0017

Cited by 4 publications

(4 citation statements)

References 122 publications

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“…It is known though that transcribed portions of genes occupy only a small fraction of TADs length ( 2 ) and therefore RNA polymerases would not be able to drive extrusion of chromatin loops larger than individual genes. There are many other motor proteins that can act as DNA translocases ( 28 ) and they could push cohesin rings over entire TADs. However, these DNA translocases would need to ‘know’ in which direction they should push the cohesin rings so that the loop growth would end up at TADs borders and would not take too much time.…”

Section: Introductionmentioning

confidence: 99%

Transcription-induced supercoiling as the driving force of chromatin loop extrusion during formation of TADs in interphase chromosomes

Račko

Benedetti

Dorier

et al. 2017

Nucleic Acids Research

112

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Using molecular dynamics simulations, we show here that growing plectonemes resulting from transcription-induced supercoiling have the ability to actively push cohesin rings along chromatin fibres. The pushing direction is such that within each topologically associating domain (TAD) cohesin rings forming handcuffs move from the source of supercoiling, constituted by RNA polymerase with associated DNA topoisomerase TOP1, towards borders of TADs, where supercoiling is released by topoisomerase TOPIIB. Cohesin handcuffs are pushed by continuous flux of supercoiling that is generated by transcription and is then progressively released by action of TOPIIB located at TADs borders. Our model explains what can be the driving force of chromatin loop extrusion and how it can be ensured that loops grow quickly and in a good direction. In addition, the supercoiling-driven loop extrusion mechanism is consistent with earlier explanations proposing why TADs flanked by convergent CTCF binding sites form more stable chromatin loops than TADs flanked by divergent CTCF binding sites. We discuss the role of supercoiling in stimulating enhancer promoter contacts and propose that transcription of eRNA sends the first wave of supercoiling that can activate mRNA transcription in a given TAD.

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Section: Introductionmentioning

confidence: 99%

Transcription-induced supercoiling as the driving force of chromatin loop extrusion during formation of TADs in interphase chromosomes

Račko

Benedetti

Dorier

et al. 2017

Nucleic Acids Research

112

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“…This translocation activity of helicases drives numerous nucleic acid metabolic processes in the cell. For example, helicases that move unidirectionally along single-stranded (ss) DNA separate the strands of double-stranded (ds) DNA and aid in DNA replication and repair, whereas those tracking along dsDNA catalyze DNA recombination and genome packaging reactions [1–7]. Given their involvement and importance in practically all nucleic acid metabolic pathways, methods have been developed to understand the fundamental properties of helicases [8–12].…”

Section: Introductionmentioning

confidence: 99%

Methods to study the coupling between replicative helicase and leading-strand DNA polymerase at the replication fork

Nandakumar

Patel

2016

Methods

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Replicative helicases work closely with the replicative DNA polymerases to ensure that the genomic DNA is copied in a timely and error free manner. Both in prokaryotes and eukaryotes, the helicase and DNA polymerase enzymes are functionally and physically coupled at the leading strand replication fork and rely on each other for optimal DNA strand separation and synthesis activities. In this review, we describe pre-steady state kinetic methods to quantify the base pair unwinding-synthesis rate constant, a fundamental parameter to understand how the helicase and polymerase help each other during leading strand replication. We describe a robust method to measure the chemical step size of the helicase-polymerase complex that determines how the two motors are energetically coupled while tracking along the DNA. The 2-aminopurine fluorescence-based methods provide structural information on the leading strand helicase-polymerase complex, such as the distance between the two enzymes, their relative positions at the replication fork, and their roles in fork junction melting. The combined information garnered from these methods informs on the mutual dependencies between the helicase and DNA polymerase enzymes, their stepping mechanism, and their individual functions at the replication fork during leading strand replication.

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“…It is also common that the affinities of these motors for binding nucleotide and binding the translocation substrate are allosterically linked to each other [49][50][51]. In fact, the regulation of substrate binding affinity by differences in the affinity of binding ATP and ADP forms the basis of some models for processive translocation by these motors [51,52]. Specifically, variations in the affinity of substrate binding within the ATPase cycle (associated with ATP, ADP, or no nucleotide bound by the motor) allows the motor to dissociate from and rebind to the translo- concentrations of the macromolecules involved in the interaction (or with the concentrations of other macromolecules in the solution)?…”

Section: Discussionmentioning

confidence: 99%

Proteins are Not Recruited: A Plea for Better Diction

Grotemeyer¹,

Briggs²,

Fischer³

2019

Emerging Trends Kinet Thermodyn

Self Cite

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Nearly all biological processes proceed or are controlled by protein-protein or protein-ligand binding reactions. Using anthropomorphic language to describe these interactions conveys an incorrect physical description of these processes while simultaneously minimizing the importance of the thermodynamics underpinning the associated interactions. Indeed, we should never say that proteins are recruited to binding partners or binding sites since this implies both a nonexistent level of communication within biological systems and a non-existent process by which proteins or binding sites actively seek other proteins. Both of these fictions hinder our ability to determine quantitatively or qualitatively distinct biophysical descriptions of the associated systems. Here we present examples of how interactions typically described as protein recruitment can be more accurately and often more simply described as variations within binding equilibria. We argue that this approach is better for describing protein-protein and protein-ligand binding, even when the objective is only a qualitative description, especially for discussions with students in courses and research groups as it provides testable models for these interactions.

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All motors have to decide is what to do with the DNA that is given them

Cited by 4 publications

References 122 publications

Transcription-induced supercoiling as the driving force of chromatin loop extrusion during formation of TADs in interphase chromosomes

Transcription-induced supercoiling as the driving force of chromatin loop extrusion during formation of TADs in interphase chromosomes

Methods to study the coupling between replicative helicase and leading-strand DNA polymerase at the replication fork

Proteins are Not Recruited: A Plea for Better Diction

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