DNA strand break: Structural and electrostatic properties studied by molecular dynamics simulation

Bunta, Juraj Kotulic; Laaksonen, Aatto; Pinák, Miroslav; Nemoto, Toshiyuki

doi:10.1016/j.compbiolchem.2005.12.001

Cited by 5 publications

(4 citation statements)

References 6 publications

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“…We suggest that the selection between the two closely separated conformers is defined by a local and transient change of ionic conditions. The results of the high dynamics of the HJ with a nick are consistent with the analysis of the effect of SSB on the structure of the DNA duplex (29)(30)(31). They show that the SSB has a minor influence on the conformation of the DNA duplex, but affects the duplex dynamics by increasing the flexibility in the proximity of the SSB.…”

Section: Discussionsupporting

confidence: 83%

Effect of Single-Strand Break on Branch Migration and Folding Dynamics of Holliday Junctions

Palets

Lushnikov

Karymov

et al. 2010

Biophysical Journal

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The Holliday junction (HJ), or four-way junction, is a central intermediate state of DNA for homologous genetic recombination and other genetic processes such as replication and repair. Branch migration is the process by which the exchange of homologous DNA regions occurs, and it can be spontaneous or driven by proteins. Unfolding of the HJ is required for branch migration. Our previous single-molecule fluorescence studies led to a model according to which branch migration is a stepwise process consisting of consecutive migration and folding steps. Folding of the HJ in one of the folded conformations terminates the branch migration phase. At the same time, in the unfolded state HJ rapidly migrates over entire homology region of the HJ in one hop. This process can be affected by irregularities in the DNA double helical structure, so mismatches almost terminate a spontaneous branch migration. Single-stranded breaks or nicks are the most ubiquitous defects in the DNA helix; however, to date, their effect on the HJ branch migration has not been studied. In addition, although nicked HJs are specific substrates for a number of enzymes involved in DNA recombination and repair, the role of this substrate specificity remains unclear. Our main goal in this work was to study the effect of nicks on the efficiency of HJ branch migration and the dynamics of the HJ. To accomplish this goal, we applied two single-molecule methods: atomic force microscopy and fluorescence resonance energy transfer. The atomic force microscopy data show that the nick does not prevent branch migration, but it does decrease the probability that the HJ will pass the DNA lesion. The single-molecule fluorescence resonance energy transfer approaches were instrumental in detailing the effects of nicks. These studies reveal a dramatic change of the HJ dynamics. The nick changes the structure and conformational dynamics of the junctions, leading to conformations with geometries that are different from those for the intact HJ. On the basis of these data, we propose a model of branch migration in which the propensity of the junction to unfold decreases the lifetimes of folded states, thereby increasing the frequency of junction fluctuations between the folded states.

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Section: Discussionsupporting

confidence: 83%

Effect of Single-Strand Break on Branch Migration and Folding Dynamics of Holliday Junctions

Palets

Lushnikov

Karymov

et al. 2010

Biophysical Journal

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“…MD simulation has shown that the presence of 3 0 -hydroxy and 5 0 -phosphate groups at the nick attract each other due to the formation of a hydrogen bond. 10 On the other hand, gel electrophoresis, UV melting measurement, and NMR have shown that the presence of a phosphate group at a nick brought about end-fraying because of electrostatic repulsion between the terminal phosphate and backbone phosphate.11-13 Whether 5 0 -phosphorylation stabilizes the nick structure or not remains unclear. In order to prepare stable DNA multiassemblies, not only complementary base-pairing of the sticky-end but also the stabilization of nicks is required.…”

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confidence: 99%

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confidence: 99%

Stabilization of DNA Multiassembly by Addition of a Phosphate Group at the 5′-Sticky End

Tanaka¹,

Matsuo²,

Niikura³

et al. 2008

Chemistry Letters

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The effect of 5 0 -phosphorylation at nicks on DNA stabilization was measured through the formation of DNA multiassemblies consisting of 40-mer half-sliding complementary oligonucleotides, which had overlapping complementary 20-mer base sequences. 5 0 -Phosphorylated oligonucleotides formed longer DNA multiassemblies than 5 0 -hydroxylated ones. This result indicated that the 5 0 -phosphorylated sticky ends contribute to the stabilization of the DNA association due to the hydrogen bonds between 3 0 -hydroxy groups and 5 0 -phosphate groups at the nick positions.DNA nanotechnology has attracted a great deal of attention as DNA has a well-defined geometry and highly predictable, diverse, and programmable hybridization.1,2 Through these DNA properties, various DNA multiassemblies; for example, nanoscaled tiles, cubes, and machines, have been fabricated. [3][4][5] In addition, the arrangement of functional materials based on DNA multiassembly via DNA hybridization has been accomplished. 6,7 Since most DNA multiassemblies are prepared through association with sticky-ended DNA, DNA assemblies are known to contain a large number of single-stranded breaks (nicks). The stability of these nicks influence the total stability of the DNA multiassemblies. The effect of 5 0 -phosphorylation on the stability of the nicks has been investigated from the view point of DNA repair process.8 XRD results have shown that the 5 0 -hydroxy group stabilize nicks by forming of a hydrogen bond with the 3 0 -hydroxy group of neighboring DNA. 9 In the case of 5 0 -phosphorylated DNA, two opposite results have been reported. MD simulation has shown that the presence of 3 0 -hydroxy and 5 0 -phosphate groups at the nick attract each other due to the formation of a hydrogen bond. 10 On the other hand, gel electrophoresis, UV melting measurement, and NMR have shown that the presence of a phosphate group at a nick brought about end-fraying because of electrostatic repulsion between the terminal phosphate and backbone phosphate.11-13 Whether 5 0 -phosphorylation stabilizes the nick structure or not remains unclear. In order to prepare stable DNA multiassemblies, not only complementary base-pairing of the sticky-end but also the stabilization of nicks is required. We found 5 0 -phosphorylation of sticky-ended DNA induces formation of a stable long DNA multi-assembly.Herein, we investigated the influence of 5 0 -phosphorylation on the formation of a one-dimensional DNA multiassembly consisting of four kinds of 40-mer half-sliding complementary oligonucleotides, A, B, pA, and pB, which had overlapping complementary 20-mer base sequences (Figure 1: 5 0 -phosphorylation is abbreviated to ''p.'' The base sequences are 5 0 -TTATGTTGTCTTGCAATACAAATGTTCTTCGAGTACTT-AT-3 0 (A or pA) and 5 0 -TGTATTGCAAGACAACATAAA-TAAGTACTCGAAGAACATT-3 0 (B or pB)). This DNA multiassembly can be regarded as an example of pseudo-addition polymerization. The reaction of the active end of the oligonucleotides monomer in the pseudo-addition polymerization results in the hybridizat...

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“…Computer modeling and simulation are quite effective in clarifying the mechanism of radiation effects because a phenomenon taking place in a small region Data Science Journal, Volume 6, Supplement, 10 May 2007 S278 in a very short time can be observed, which is difficult to examine by experimental approaches. As explained above, the size of the problem is very large, and thus we classified it into three different sized problems, from phenomenological view points: 1) DNA strand breakage by ionizing radiation (Watanabe & Saito, 2002), 2) DNA lesion repair (Bunta, Laaksonen, Pinak, & Nemoto, 2006), and 3) the process of cell carcinogenesis and tumorigenesis. Hereafter, we mainly focus on the third problem, the modeling and simulation of cell carcinogenesis and tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

Computer Modeling of Radiation Effects

Ouchi

2007

Data Sci. J.

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DNA strand break: Structural and electrostatic properties studied by molecular dynamics simulation

Cited by 5 publications

References 6 publications

Effect of Single-Strand Break on Branch Migration and Folding Dynamics of Holliday Junctions

Effect of Single-Strand Break on Branch Migration and Folding Dynamics of Holliday Junctions

Stabilization of DNA Multiassembly by Addition of a Phosphate Group at the 5′-Sticky End

Computer Modeling of Radiation Effects

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