Effects of Molecular Crowding on the Structures, Interactions, and Functions of Nucleic Acids

Nakano, Shu-ichi; Miyoshi, Daisuke; Sugimoto, Naoki

doi:10.1021/cr400113m

Cited by 457 publications

(481 citation statements)

References 365 publications

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“…The intracellular dielectric constant has been predicted in the range 3055. 6 In our system, the effects of crowders on photoinduced ET were observed even in the mediums with higher dielectric constants. These results suggest that the DNA-mediated ET in intracellular environments has a wide variety according to the situation.…”

Section: •+mentioning

confidence: 64%

“…22 In addition, lower water activity under crowding conditions 6,13 may affect the reaction between G…”

Section: •+mentioning

confidence: 99%

“…Crowding by biomolecules causes changes in structures and stabilities of DNA as well as enzymatic reactivities to DNA. 6 Thus, DNA-mediated ET and DNA oxidative damages will also be affected by large amounts of coexisting molecules that change molecular diffusion rates, associations of molecules, solvent polarity, and water activity. Herein we investigated the effect of the surrounding medium on DNA damage via photoinduced ET using pyrene-modified oligonucleotides and found that molecular crowding mediums affected the efficiency of oxidative damage and the path of photoinduced ET in DNA.…”

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confidence: 99%

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Effects of Molecular-crowding on Electron Transfer and Oxidative Damage in Pyrene-modified Oligonucleotides

2018

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We examined guanine damages caused by photoinduced electron transfer (ET) in biomimetic environments using pyrenemodified oligonucleotides and molecular crowders. As a result, guanine damage induced by ET in full-matched DNA was decreased under viscous crowding conditions. On the other hand, behaviors of mismatched DNA revealed that throughspace ET between pyrene moiety and the consecutive guanine site was promoted under molecular-crowding conditions.Keywords: Guanine damage | DNA-mediated electron transfer | Molecular crowdingMechanisms of electron transfer (ET) through double helical DNA have been elucidated by extensive studies using electron donors and acceptors bound to DNA.1 It is well known that a hole injected by a photooxidant moves through base stacking and oxidizes DNA at a guanine (G) site, which is the most easily oxidized base. Oxidative damage within the genome is one of the important themes involving DNA-mediated ET.2 DNAmediated ET within the nucleosome structure has been examined by a rhodium intercalator 3 and an anthraquinone 4 as photooxidants. Moreover, a recent study revealed that DNA-mediated ET played an important role in primase functions.5 To clarify chemical roles of ET in vivo, we need to study DNA-mediated ET under crowded conditions, because the intracellular environment is highly crowded with 2040 wt % various biomolecules. Crowding by biomolecules causes changes in structures and stabilities of DNA as well as enzymatic reactivities to DNA. 6 Thus, DNA-mediated ET and DNA oxidative damages will also be affected by large amounts of coexisting molecules that change molecular diffusion rates, associations of molecules, solvent polarity, and water activity. Herein we investigated the effect of the surrounding medium on DNA damage via photoinduced ET using pyrene-modified oligonucleotides and found that molecular crowding mediums affected the efficiency of oxidative damage and the path of photoinduced ET in DNA.In this study, 5-(pyrenylethynyl)-2¤-deoxyuridine ( Py U) was used as a hole injector in DNA. The photoexcited Py U works as both hole and electron injectors for DNA-mediated ET.79 ET initiated by hole injection from the excited Py U can be evaluated by decomposition of guanines under air. It is advantageous for the study that the alkynylpyrene moiety of Py U is hardly quenched by oxygen and has long absorption wavelength. 10DNA sequences used in this investigation are shown in Figure 1. A pyrene molecule incorporated onto the 5-position of uracil via ethynyl linkage is located in DNA major groove, thus maintaining the the hydrogen bonding with adenine. 7 The DNA strands were designed to examine molecular-crowding effects on intrastrand ET in DNA. As DNA I, three adenines are embedded between Py U and GG. Continuous guanine (G) site 11 with the lowest oxidation potential is considered to trap a hole injected from the excited Py U via DNA-mediated ET and to generate guanine radical cation (G •+ ) at the GG site. Other guanines paired with C were replaced by inosines (inosine, I),...

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Section: •+mentioning

confidence: 64%

“…22 In addition, lower water activity under crowding conditions 6,13 may affect the reaction between G…”

Section: •+mentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of Molecular-crowding on Electron Transfer and Oxidative Damage in Pyrene-modified Oligonucleotides

2018

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“…Furthermore, the additives may directly interact with nucleic acids, and additives of large size occupy large volumes from which other molecules are excluded. These factors potentially influence the thermodynamics and kinetics of nucleic acid interactions [20]. Results show that the ribozymes and DNAzymes used in this study remain active in many mixed solutions, and they may even display enhanced catalytic activity.…”

Section: Introductionmentioning

confidence: 92%

“…These organic additives may alter the physical properties of solution, interact with nucleic acids, and introduce areas of excluded volume [20,31]. Most mixed solutions have lower dielectric constant values than pure water, and the additives, such as large PEGs, MME, DME, EtOH PrOH, and DOX, significantly lowers the dielectric constant of solution.…”

Section: Classification Of the Mixed Solutions Based On The Effects Omentioning

confidence: 99%

Catalytic Activities of Ribozymes and DNAzymes in Water and Mixed Aqueous Media

2017

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Catalytic nucleic acids are regarded as potential therapeutic agents and biosensors. The catalytic activities of nucleic acid enzymes are usually investigated in dilute aqueous solutions, although the physical properties of the reaction environment inside living cells and that in the area proximal to the surface of biosensors in which they operate are quite different from those of pure water. The effect of the molecular environment is also an important focus of research aimed at improving and expanding nucleic acid function by addition of organic solvents to aqueous solutions. In this study, the catalytic activities of RNA and DNA enzymes (hammerhead ribozyme, 17E DNAzyme, R3C ribozyme, and 9DB1 DNAzyme) were investigated using 21 different mixed aqueous solutions comprising organic compounds. Kinetic measurements indicated that these enzymes can display enhanced catalytic activity in mixed solutions with respect to the solution containing no organic additives. Correlation analyses revealed that the turnover rate of the reaction catalyzed by hammerhead ribozyme increased in a medium with a lower dielectric constant than water, and the turnover rate of the reaction catalyzed by 17E DNAzyme increased in conditions that increased the strength of DNA interactions. On the other hand, R3C ribozyme and 9DB1 DNAzyme displayed no significant turnover activity, but their single-turnover rates increased in many mixed solutions. Our data provide insight into the activity of catalytic nucleic acids under various conditions that are applicable to the medical and technology fields, such as in living cells and in biosensors.

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Advances in the cellular structural biology of nucleic acids

et al. 2018

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Conventional biophysical and chemical biology approaches for delineating relationships between the structure and biological function of nucleic acids (NAs) abstract NAs from their native biological context. However, cumulative experimental observations have revealed that the structure, dynamics and interactions of NAs might be strongly influenced by a broad spectrum of specific and nonspecific physical-chemical environmental factors. This consideration has recently sparked interest in the development of novel tools for structural characterization of NAs in the native cellular context. Here, we review the individual methods currently being employed for structural characterization of NA structure in a native cellular environment with a focus on recent advances and developments in the emerging fields of in-cell NMR and electron paramagnetic resonance spectroscopy and in-cell single-molecule FRET of NAs.

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Effects of Molecular Crowding on the Structures, Interactions, and Functions of Nucleic Acids

Cited by 457 publications

References 365 publications

Effects of Molecular-crowding on Electron Transfer and Oxidative Damage in Pyrene-modified Oligonucleotides

Effects of Molecular-crowding on Electron Transfer and Oxidative Damage in Pyrene-modified Oligonucleotides

Catalytic Activities of Ribozymes and DNAzymes in Water and Mixed Aqueous Media

Advances in the cellular structural biology of nucleic acids

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