DNA Double Helices Recognize Mutual Sequence Homology in a Protein Free Environment

Baldwin, Geoff; Brooks, Nicholas J.; Robson, Rebecca E.; Wynveen, A.; Goldar, Arach; Leikin, Sergey; Seddon, John M.; Kornyshev, Alexei A.

doi:10.1021/jp7112297

Cited by 75 publications

(128 citation statements)

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“…Performed deliberately in a ''test tube'' and in a pure electrolytic solution (28), they have demonstrated that recognition may be warranted by a physical phenomenon that may result solely from the underlying structure of DNA. Still, those experiments are only a first step.…”

Section: Discussionmentioning

confidence: 99%

“…Current estimate of c based on X-ray data from wet fibers or NMR data banks in solution is Ϸ100 Å (27). Homology recognition between intact DNA duplexes in proteinfree electrolytic solutions has been demonstrated by Baldwin et al (28). In that work a mixture of 2 fluorescently tagged double-helical DNAs with identical nucleotide composition and length, but different sequences, was studied.…”

Section: Homology Recognition Enigmamentioning

confidence: 99%

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The homology recognition well as an innate property of DNA structure

Kornyshev

Wynveen

2009

Proc. Natl. Acad. Sci. U.S.A.

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Mutual recognition of homologous sequences of DNA before strand exchange is considered to be the most puzzling stage of recombination of genes. In 2001, a mechanism was suggested for a doublestranded DNA molecule to recognize from a distance its homologous match in electrolytic solution without unzipping [Kornyshev AA, Leikin S (2001) Phys Rev Lett 86:3666 -3669]. Based on a theory of electrostatic interactions between helical molecules, the difference in the electrostatic interaction energy between homologous duplexes and between nonhomologous duplexes, called the recognition energy, was calculated. Here, we report a theoretical investigation of the form of the potential well that DNA molecules may feel sliding along each other. This well, the bottom of which is determined by the recognition energy, leads to trapping of the molecular tracks of the same homology in direct juxtaposition. A simple formula for the shape of the well is obtained. The well is quasi-exponential. Its half-width is determined by the helical coherence length, introduced first in the same 2001 article, the value of which, as the latest study shows, is Ϸ10 nm.Decades of research into homologous recombination have unraveled many of the details concerning the transfer of information between 2 homologous sequences. By contrast, the processes by which the interacting molecules initially colocalize are largely unknown. How can 2 homologous needles find each other in the genomic haystack?- Barzel and Kupiec (2008) R ecombination of genes is a process in which sequences are exchanged between 2 DNA molecules. In homologous recombination fragments of the same homology, those that have almost identical sequences are swapped. This makes possible gene shuffling between 2 parental copies of DNA, crucial for evolution and genetic diversity. A similar process is used in DNA repair, when the cell uses a backup copy of the genome as a template for repairs. It is generally accepted that understanding recombination of genes is one of the key challenges of the ''postgenomic era'' (1). Homology Recognition EnigmaThe key point in homologous recombination is the swapping of correct genes: only regions with homologous sequences should be exchanged or used as a template for repair. Recombination mistakes are known to cause a variety of severe genetic diseases (2, 3) and contribute to aging (4). Fortunately, such errors are rare. The recognition of sequence homology occurs with amazing precision. In site-specific recombination, the exchange happens at specific, designated loci recognized by the complex recombination machinery of the cell (involving multiple proteins). In homologous recombination the exchange can occur anywhere. It was established that at least 50-to 100-bp homology is required for it (see, e.g., refs. 5-7). This ensures that the fragments belong to 2 alleles of the same gene rather than to different genes. The long-range goal is an in-depth understanding of the recognition mechanism to be able to develop procedures that could further minimize these ...

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Section: Discussionmentioning

confidence: 99%

Section: Homology Recognition Enigmamentioning

confidence: 99%

The homology recognition well as an innate property of DNA structure

Kornyshev

Wynveen

2009

Proc. Natl. Acad. Sci. U.S.A.

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“…5. Baldwin et al (2008) discussed two chains of DNA with identical nucleotide structure that experience an attraction to each other. However, the physical mechanism of attraction remains unclear.…”

Section: Possible Experiments To Test the Hypothesismentioning

confidence: 99%

Biological complexity, quantum coherent states and the problem of efficient transmission of information inside a cell

Melkikh

2013

Biosystems

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a b s t r a c tThe intracellular channel of information transmission was analyzed from the point of view of complexity. The most important steps in the transfer of information within a cell are the folding, transport and recognition of proteins. It was shown that the large number of conformational degrees of freedom that proteins possess can paradoxically lead to an information channel with an exponentially small capacity. To resolve this paradox, a model, which assumes a quantum collective behavior of biologically important molecules, was proposed. Experiments to test the quantum nature of the intracellular transfer of information were also proposed.

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“…These suggest a possible role for direct interactions between double stranded DNA in the homologous pairing process. The experiments utilized gel electrophoresis, 37 cholesteric liquid crystals, 38 AFM imaging, 39 and surface-confined DNA using magnetic beads. 40 In addition, Seeman's group reported the formation of PX-DNA complexes presumably resulting from homologue pairing, 41 and homology recognition has also been observed between nucleosomes.…”

Section: Introductionmentioning

confidence: 99%

Which way up? Recognition of homologous DNA segments in parallel and antiparallel alignments

Lee

Wynveen

Albrecht

et al. 2015

The Journal of Chemical Physics

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Homologous gene shuffling between DNA molecules promotes genetic diversity and is an important pathway for DNA repair. For this to occur, homologous genes need to find and recognize each other. However, despite its central role in homologous recombination, the mechanism of homology recognition has remained an unsolved puzzle of molecular biology. While specific proteins are known to play a role at later stages of recombination, an initial coarse grained recognition step has, however, been proposed. This relies on the sequence dependence of the DNA structural parameters, such as twist and rise, mediated by intermolecular interactions, in particular, electrostatic ones. In this proposed mechanism, sequences that have the same base pair text, or are homologous, have lower interaction energy than those sequences with uncorrelated base pair texts. The difference between the two energies is termed the "recognition energy." Here, we probe how the recognition energy changes when one DNA fragment slides past another, and consider, for the first time, homologous sequences in antiparallel alignment. This dependence on sliding is termed the "recognition well." We find there is a recognition well for anti-parallel, homologous DNA tracts, but only a very shallow one, so that their interaction will differ little from the interaction between two nonhomologous tracts. This fact may be utilized in single molecule experiments specially targeted to test the theory. As well as this, we test previous theoretical approximations in calculating the recognition well for parallel molecules against MC simulations and consider more rigorously the optimization of the orientations of the fragments about their long axes upon calculating these recognition energies. The more rigorous treatment affects the recognition energy a little, when the molecules are considered rigid. When torsional flexibility of the DNA molecules is introduced, we find excellent agreement between the analytical approximation and simulations. C 2015 AIP Publishing LLC. [http://dx

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DNA Double Helices Recognize Mutual Sequence Homology in a Protein Free Environment

Cited by 75 publications

References 24 publications

The homology recognition well as an innate property of DNA structure

The homology recognition well as an innate property of DNA structure

Biological complexity, quantum coherent states and the problem of efficient transmission of information inside a cell

Which way up? Recognition of homologous DNA segments in parallel and antiparallel alignments

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