How to accelerate protein search on DNA: Location and dissociation

Kolomeisky, Anatoly B.; Veksler, Alex

doi:10.1063/1.3697763

Cited by 31 publications

(60 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The discrete-state stochastic approach 15,16 can be generalized for analyzing the protein search with arbitrary number of targets and traps on DNA. To capture the main features of the process, we consider a simpler model where a single protein molecule searches for one specific binding site on a single DNA chain, which also has one semispecific binding site, as presented in Fig.…”

Section: Theoretical Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Dynamics of the Protein Search for Targets on DNA in the Presence of Traps

2015

Self Cite

View full text Add to dashboard Cite

Protein search for specific binding sites on DNA is a fundamental biological phenomenon associated with the beginning of most major biological processes. It is frequently found that proteins find and recognize their specific targets quickly and efficiently despite the complex nature of protein-DNA interactions in living cells. Although significant experimental and theoretical efforts was made in recent years, the mechanisms of these processes remain not well clarified. We present a theoretical study of the protein target search dynamics in the presence of semi-specific binding sites which are viewed as traps. Our theoretical approach employs a discrete-state stochastic method that accounts for the most important physical and chemical processes in the system. It also leads to a full analytical description for all dynamic properties of the protein search. It is found that the presence of traps can significantly modify the protein search dynamics. This effect depends on the spatial positions of the targets and traps, on distances between them, on the average sliding length of the protein along the DNA, and on the total length of DNA. Theoretical predictions are discussed using simple physical-chemical arguments, and they are also validated with extensive Monte Carlo computer simulations.keywords: protein-DNA interactions, discrete-state stochastic models, first-passage processes 2

show abstract

Section: Theoretical Methodsmentioning

confidence: 99%

“…Our analysis uses a discrete-state stochastic approach 15,16 that explicitly takes into consideration major physical and chemical processes in the system. It allows us to obtain a full analytical description for all dynamic properties in the protein search by utilizing a method of first-passage processes.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of the Protein Search for Targets on DNA in the Presence of Traps

2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…This suggests to employ a first-passage method of analyzing the dynamic properties, which turned out to be very successful in analyzing various protein search phenomena (25,26,30,31). We introduce functions F (0) n (t) and F (1) n (t), defined as the probability density functions to reach the target at time t for the first time, if initially at t = 0 the RecA filament starts at the site n (i) (n = 0, 1, .…”

Section: Theoretical Modelmentioning

confidence: 99%

“…It is based on the idea related to the intersegmental contact sampling mechanism, and the model argues that the RecA nucleoprotein filament can scan DNA faster for more coiled DNA conformations. Our analysis extends the earlier developed discrete-state stochastic approach for protein search for targets on DNA (25,26), which explicitly takes into consideration major physical and chemical processes in the system. This allows us to obtain a full analytical description for all dynamic properties of the homology search by utilizing a method of first-passage probabilities (26).…”

Section: Introductionmentioning

confidence: 96%

“…By now, it is well proven that the homology search is not an active process since ATP hydrolysis is not required to proceed forward (17,18). Therefore, it must be related to protein search for targets on DNA that have been intensively investigated in recent years (23)(24)(25)(26)(27)(28)(29)(30). However, a comprehensive description of the mechanisms of the homology search still does not exist even for simplified in vitro systems.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

On the Mechanism of Homology Search by RecA Protein Filaments

Kochugaeva

Shvets

Kolomeisky

2017

Biophysical Journal

Self Cite

View full text Add to dashboard Cite

Genetic stability is a key factor in maintaining, survival and reproduction of biological cells. It relies on many processes, but one of the most important is a homologous recombination, in which the repair of breaks in double-stranded DNA molecules is taking place with a help of several specific proteins. In bacteria this task is accomplished by RecA proteins that are active as nucleoprotein filaments formed on single-stranded segments of DNA. A critical step in the homologous recombination is a search for a corresponding homologous region on DNA, which is called a homology search. Recent single-molecule experiments clarified some aspects of this process, but its molecular mechanisms remain not well understood. We developed a quantitative theoretical approach to analyze the homology search. It is based on a discrete-state stochastic model that takes into account the most relevant physical-chemical processes in the system. Using a method of first-passage processes, a full dynamic description of the homology search is presented. It is found that the search dynamics depends on the degree of extension of DNA molecules and on the size of RecA nucleoprotein filaments, in agreement with experimental single-molecule measurements of DNA pairing by RecA proteins. Our theoretical calculations, supported by extensive Monte Carlo computer simulations, provide a molecular description of the mechanisms of the homology search.

show abstract

Positive and Negative Design for Nonconsensus Protein-DNA Binding Affinity in the Vicinity of Functional Binding Sites

Afek

Lukatsky

2013

Biophysical Journal

View full text Add to dashboard Cite

Recent experiments provide an unprecedented view of protein-DNA binding in yeast and human genomes at single-nucleotide resolution. These measurements, performed over large cell populations, show quite generally that sequence-specific transcription regulators with well-defined protein-DNA consensus motifs bind only a fraction among all consensus motifs present in the genome. Alternatively, proteins in vivo often bind DNA regions lacking known consensus sequences. The rules determining whether a consensus motif is functional remain incompletely understood. Here we predict that genomic background surrounding specific protein-DNA binding motifs statistically modulates the binding of sequence-specific transcription regulators to these motifs. In particular, we show that nonconsensus protein-DNA binding in yeast is statistically enhanced, on average, around functional Reb1 motifs that are bound as compared to nonfunctional Reb1 motifs that are unbound. The landscape of nonconsensus protein-DNA binding around functional CTCF motifs in human demonstrates a more complex behavior. In particular, human genomic regions characterized by the highest CTCF occupancy, show statistically reduced level of nonconsensus protein-DNA binding. Our findings suggest that nonconsensus protein-DNA binding is fine-tuned around functional binding sites using a variety of design strategies.

show abstract

How to accelerate protein search on DNA: Location and dissociation

Cited by 31 publications

References 34 publications

Dynamics of the Protein Search for Targets on DNA in the Presence of Traps

Dynamics of the Protein Search for Targets on DNA in the Presence of Traps

On the Mechanism of Homology Search by RecA Protein Filaments

Positive and Negative Design for Nonconsensus Protein-DNA Binding Affinity in the Vicinity of Functional Binding Sites

Contact Info

Product

Resources

About