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A wide range of cellular processes initiates upon recognising and binding of proteins to specific DNA sites. Typically, the recognition process is incredibly fast owing to a complex mechanism that combines different 3D and 1D modes of translocation of the protein. While few studies performed on selected DNA topologies suggested that the DNA topology might alter the balance between these two modes and therefore the target search kinetics, its detail role in target search mechanism remains unclear. Here, we present a discrete-state stochastic approach that allows us to incorporate the topological information of DNA molecule explicitly and predict its role during the process when proteins search for their specific binding sites on DNA. Applying the theory to the closed loop and different supercoiled DNA topologies, we find that the target search efficiency of the protein is strongly influenced by the DNA topology. Furthermore, if the topology is such that it promotes juxtaposition of distant DNA sites, the number, position and relative distances between such juxtaposition sites play a crucial role in facilitating the search process by providing additional routes to approach the target site. Our predictions are validated through extensive Monte Carlo simulations.
This article was published in the following journal.
Name: The journal of physical chemistry. B
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Homer proteins belong to a family of adaptor and scaffold proteins which include Homer1, Homer2 and Homer3. Homer1 and Homer2 play a role in the regulation of calcium homeostasis, whereas Homer3 functions in stimulating changes in actin dynamics in neurons and T-cells. Homer proteins are best known as scaffold proteins at the post-synaptic density where they facilitate synaptic signaling. They function as a molecular switch in metabotropic glutamate receptor (MGluR) signaling, and are associated with human Fragile X syndrome.
Proteins obtained from the species Schizosaccharomyces pombe. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
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The act or fact of grasping the meaning, nature, or importance of; understanding. (American Heritage Dictionary, 4th ed) Includes understanding by a patient or research subject of information disclosed orally or in writing.
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