The effects of loop size on Sac7d-hairpin DNA interactions

Yuann, Jeu-Ming P.; Tseng, Wen-Hsuan; Lin, Hsin-Ying; Hou, Ming-Hon

doi:10.1016/j.bbapap.2012.05.011

Cited by 10 publications

(5 citation statements)

References 42 publications

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“…In general, these changes are assumed to be proportional to the mass of the molecules bound to the chip and are recorded in resonance units (RU) (23). The 5′-biotin-labelled hairpin DNA duplexes used in the SPR experiments were purified by polyacrylamide gel electrophoresis.…”

Section: Methodsmentioning

confidence: 99%

The structural basis of actinomycin D–binding induces nucleotide flipping out, a sharp bend and a left-handed twist in CGG triplet repeats

Tseng

Chuang

et al. 2013

Nucleic Acids Research

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The potent anticancer drug actinomycin D (ActD) functions by intercalating into DNA at GpC sites, thereby interrupting essential biological processes including replication and transcription. Certain neurological diseases are correlated with the expansion of (CGG)n trinucleotide sequences, which contain many contiguous GpC sites separated by a single G:G mispair. To characterize the binding of ActD to CGG triplet repeat sequences, the structural basis for the strong binding of ActD to neighbouring GpC sites flanking a G:G mismatch has been determined based on the crystal structure of ActD bound to ATGCGGCAT, which contains a CGG triplet sequence. The binding of ActD molecules to GCGGC causes many unexpected conformational changes including nucleotide flipping out, a sharp bend and a left-handed twist in the DNA helix via a two site-binding model. Heat denaturation, circular dichroism and surface plasmon resonance analyses showed that adjacent GpC sequences flanking a G:G mismatch are preferred ActD-binding sites. In addition, ActD was shown to bind the hairpin conformation of (CGG)16 in a pairwise combination and with greater stability than that of other DNA intercalators. Our results provide evidence of a possible biological consequence of ActD binding to CGG triplet repeat sequences.

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Section: Methodsmentioning

confidence: 99%

The structural basis of actinomycin D–binding induces nucleotide flipping out, a sharp bend and a left-handed twist in CGG triplet repeats

Tseng

Chuang

et al. 2013

Nucleic Acids Research

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“…The T m were evaluated directly from the temperature at f = 0.5. The thermodynamic parameters of DNA with and without ACTD in the presence of spermine at various concentrations were estimated using the melting profiles according to a previously described method [35], [36].…”

Section: Methodsmentioning

confidence: 99%

Spermine Attenuates the Action of the DNA Intercalator, Actinomycin D, on DNA Binding and the Inhibition of Transcription and DNA Replication

et al. 2012

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The anticancer activity of DNA intercalators is related to their ability to intercalate into the DNA duplex with high affinity, thereby interfering with DNA replication and transcription. Polyamines (spermine in particular) are almost exclusively bound to nucleic acids and are involved in many cellular processes that require nucleic acids. Until now, the effects of polyamines on DNA intercalator activities have remained unclear because intercalation is the most important mechanism employed by DNA-binding drugs. Herein, using actinomycin D (ACTD) as a model, we have attempted to elucidate the effects of spermine on the action of ACTD, including its DNA-binding ability, RNA and DNA polymerase interference, and its role in the transcription and replication inhibition of ACTD within cells. We found that spermine interfered with the binding and stabilization of ACTD to DNA. The presence of increasing concentrations of spermine enhanced the transcriptional and replication activities of RNA and DNA polymerases, respectively, in vitro treated with ActD. Moreover, a decrease in intracellular polyamine concentrations stimulated by methylglyoxal-bis(guanylhydrazone) (MGBG) enhanced the ACTD-induced inhibition of c-myc transcription and DNA replication in several cancer cell lines. The results indicated that spermine attenuates ACTD binding to DNA and its inhibition of transcription and DNA replication both in vitro and within cells. Finally, a synergistic antiproliferative effect of MGBG and ACTD was observed in a cell viability assay. Our findings will be of significant relevance to future developments in combination with cancer therapy by enhancing the anticancer activity of DNA interactors through polyamine depletion.

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“…GH5 with hairpin structure showed a positive peak near 270 nm and a negative peak near 245 nm, which indicated a B-form. 24 Addition of terbium ions did not change the CD spectra shape of GH5, which implied the hairpin structure is retained. As the terbium ions increased, the decreased of the ellipticity intensity of Tb-GH5 at both positive and negative peaks is ascribed to the interaction between terbium and guanine.…”

Section: Conformation Of Tb-gh5 Probementioning

confidence: 94%

Hairpin oligonucleotides anchored terbium ion: a fluorescent probe to specifically detect lead(ii) at sub-nM levels

Wei

Liu

Wang

et al. 2013

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A terbium based fluorescent probe was synthesized by coordinating terbium ions with a designed oligonucleotides (5'-ATATGGGGGATAT-3', termed GH5). GH5 improved the fluorescence of terbium ions by four orders of magnitude. The fluorescence enhancement of terbium ions by different oligonucleotides sequences indicated that the polyguanine loop of the hairpin GH5 is key to enhance terbium ion emission. The quantum yield of Tb-GH5 probe was 10.5% and the probe was photo-stable. The result of conductivity titration indicated that the stoichiometry of the probe is 3.5 Tb: 1 GH5, which is confirmed by fluorescence titration. This probe had high sensitivity and specificity for the detection of lead ions. The fluorescence intensity of this probe was linear with respect to lead concentration over a range 0.3-2.1 nM (R(2) = 0.99). The limit of detection for lead ions was 0.1 nM at a signal-to-noise ratio of 3.

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The effects of loop size on Sac7d-hairpin DNA interactions

Cited by 10 publications

References 42 publications

The structural basis of actinomycin D–binding induces nucleotide flipping out, a sharp bend and a left-handed twist in CGG triplet repeats

The structural basis of actinomycin D–binding induces nucleotide flipping out, a sharp bend and a left-handed twist in CGG triplet repeats

Spermine Attenuates the Action of the DNA Intercalator, Actinomycin D, on DNA Binding and the Inhibition of Transcription and DNA Replication

Hairpin oligonucleotides anchored terbium ion: a fluorescent probe to specifically detect lead(ii) at sub-nM levels

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