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.affiliation: 1] Department of Mathematics, Washington State University, Richland, WA 99354, USA [2] Department of Mechanical Engineering, Washington State University, Richland, WA 99354, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Traverso
authors.affiliation: Department of Mathematics, Washington State University, Pullman, WA 99163, USA.
authors.forename: Valipuram S
authors.initials: VS
authors.lastname: Manoranjan
authors.affiliation: Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Bishop
authors.affiliation: Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: Kim Ø
authors.initials: KØ
authors.lastname: Rasmussen
authors.affiliation: Department of Mathematics, Washington State University, Richland, WA 99354, USA.
authors.forename: Nikolaos K
authors.initials: NK
authors.lastname: Voulgarakis
mesh_terms: D000465:Algorithms; D000494:Allosteric Regulation; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D066329:Protein Aggregates; D011485:Protein Binding; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D066329:Protein Aggregates; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D004247:DNA