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Title: Allostery through protein-induced DNA bubbles

Abstract

Allostery through DNA is increasingly recognized as an important modulator of DNA functions. Here, we show that the coalescence of protein-induced DNA bubbles can mediate allosteric interactions that drive protein aggregation. We propose that such allostery may regulate DNA's flexibility and the assembly of the transcription machinery. Mitochondrial transcription factor A (TFAM), a dual-function protein involved in mitochondrial DNA (mtDNA) packaging and transcription initiation, is an ideal candidate to test such a hypothesis owing to its ability to locally unwind the double helix. Numerical simulations demonstrate that the coalescence of TFAM-induced bubbles can explain experimentally observed TFAM oligomerization. The resulting melted DNA segment, approximately 10 base pairs long, around the joints of the oligomers act as flexible hinges, which explains the efficiency of TFAM in compacting DNA. Since mitochondrial polymerase (mitoRNAP) is involved in melting the transcription bubble, TFAM may use the same allosteric interaction to both recruit mitoRNAP and initiate transcription.

Authors:
 [1];  [2];  [3];  [3];  [4]
+ Show Author Affiliations
  1. Washington State Univ., Richland, WA (United States). Dept. of Mathematics and Dept. of Mechanical Engineering.
  2. Washington State Univ., Richland, WA (United States). Dept. of Mathematics.
  3. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  4. Washington State Univ., Pullman, WA (United States). Dept. of Mathematics.
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1190537
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 5; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Traverso, Joseph J., Manoranjan, Valipuram S., Bishop, A. R., Rasmussen, Kim Ø., and Voulgarakis, Nikolaos K. Allostery through protein-induced DNA bubbles. United States: N. p., 2015. Web. doi:10.1038/srep09037.
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Traverso, Joseph J., Manoranjan, Valipuram S., Bishop, A. R., Rasmussen, Kim Ø., & Voulgarakis, Nikolaos K. Allostery through protein-induced DNA bubbles. United States. https://doi.org/10.1038/srep09037
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Traverso, Joseph J., Manoranjan, Valipuram S., Bishop, A. R., Rasmussen, Kim Ø., and Voulgarakis, Nikolaos K. Thu . "Allostery through protein-induced DNA bubbles". United States. https://doi.org/10.1038/srep09037. https://www.osti.gov/servlets/purl/1190537.
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@article{osti_1190537,
title = {Allostery through protein-induced DNA bubbles},
author = {Traverso, Joseph J. and Manoranjan, Valipuram S. and Bishop, A. R. and Rasmussen, Kim Ø. and Voulgarakis, Nikolaos K.},
abstractNote = {Allostery through DNA is increasingly recognized as an important modulator of DNA functions. Here, we show that the coalescence of protein-induced DNA bubbles can mediate allosteric interactions that drive protein aggregation. We propose that such allostery may regulate DNA's flexibility and the assembly of the transcription machinery. Mitochondrial transcription factor A (TFAM), a dual-function protein involved in mitochondrial DNA (mtDNA) packaging and transcription initiation, is an ideal candidate to test such a hypothesis owing to its ability to locally unwind the double helix. Numerical simulations demonstrate that the coalescence of TFAM-induced bubbles can explain experimentally observed TFAM oligomerization. The resulting melted DNA segment, approximately 10 base pairs long, around the joints of the oligomers act as flexible hinges, which explains the efficiency of TFAM in compacting DNA. Since mitochondrial polymerase (mitoRNAP) is involved in melting the transcription bubble, TFAM may use the same allosteric interaction to both recruit mitoRNAP and initiate transcription.},
doi = {10.1038/srep09037},
journal = {Scientific Reports},
number = ,
volume = 5,
place = {United States},
year = {Thu Mar 12 00:00:00 EDT 2015},
month = {Thu Mar 12 00:00:00 EDT 2015}
}
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https://doi.org/10.1038/srep09037
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    Works referencing / citing this record:

    Organization of DNA in Mammalian Mitochondria
    journal, June 2019

    • Farge, Géraldine; Falkenberg, Maria
    • International Journal of Molecular Sciences, Vol. 20, Issue 11
    • DOI: 10.3390/ijms20112770

    Acetylation and phosphorylation of human TFAM regulate TFAM–DNA interactions via contrasting mechanisms
    journal, March 2018

    • King, Graeme A.; Hashemi Shabestari, Maryam; Taris, Kees-Karel H.
    • Nucleic Acids Research, Vol. 46, Issue 7
    • DOI: 10.1093/nar/gky204
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