Mechanism of DNA Strand Scission Induced by (1,10-Phenanthroline)copper Complex: Major Direct DNA Cleavage Is Not through 1‘,2‘-Dehydronucleotide Intermediate nor β-Elimination of Forming Ribonolactone

Mechanism of DNA Strand Scission Induced by (1,10-Phenanthroline)copper Complex:  Major Direct DNA Cleavage Is Not through 1‘,2‘-Dehydronucleotide Intermediate nor β-Elimination of Forming Ribonolacton

Highly Efficient Photochemical 2‘-Deoxyribonolactone Formation at the Diagonal Loop of a 5-Iodouracil-Containing Antiparallel G-Quartet

To explore the structure-dependent hydrogen abstraction in antiparallel and parallel G-quartet DNA structures, the photochemical reactivity of 5-iodouracil (IU)-containing human telomeric DNA 22-mers was investigated under the 302 nm UV irradiation conditions. We discovered that only antiparallel ODN 4, in which the second T residue in the diagonal loop of the antiparallel G-quartet is substituted with IU, was rapidly consumed as compared with parallel ODN 4 and the other IU-containing 22-mers under the irradiation conditions. Product analysis of the photolyzate of antiparallel ODN 4 indicated that a 2‘-deoxyribonolactone residue was effectively produced at the 5‘ side of the IU residue in the diagonal loop. Photochemical 2‘-deoxyribonolactone formation was also found in the IU-containing diagonal loop of antiparallel G-quartets d(GGGGTTTIUGGGG)2 and d(GGGGTTIUTGGGG)2, whereas the reaction did not occur at other DNA structures, including the single-stranded form, the loop region of the hairpin, and linear four-stranded G-quartets. The results clearly indicate that this type of 2‘-deoxyribonolactone formation efficiently occurrs only in the diagonal loop of the antiparallel G-quartet. Furthermore, we found that 2‘-deoxyribonolactone was formed at the IU-containing G-rich sequence of the IgG switch regions and the 5‘ termini of the Rb gene, suggesting the formation of an antiparallel G-quartet with a diagonal loop in these sequences. These results suggest that the present photochemical method can be used as a specific probe for the antiparallel G-quartet with the diagonal loop

Unique Charge Transfer Properties of the Four-Base π-Stacks in Z-DNA

To investigate the photoreactions of BrU in Z-DNA, the photoirradiation of 5‘-d(C1G2C3G4BrU5G6C7G8)-3‘/5‘-d(C9mG10C11A12C13mG14C15G16)-3‘(ODN 1-2) was investigated. In accord with previous observations, B-form ODN 1-2 with the 5‘-GBrU sequence showed very weak photoreactivity. However, Z-form ODN 1-2 in 2 M NaCl underwent photoreaction to afford 5‘-d(CGC)rGd(UGCG)-3‘ together with the formation of imidazolone (Iz) contained 5‘-d(CIzCACmGCG)-3‘. The results clearly indicate that structural changes caused by the B−Z transition dramatically increased the photoreactivity of ODN 1-2. Inspection of the molecular structure of Z-DNA suggests that there is unique four-base π-stacks at the G4-BrU5-C11-mG10 in ODN 1-2. These results suggest that the intriguing possibility that the mG10 in a complementary strand located at the end of the four-base π-stacks may act as an electron donor. To test the hypothesis of interstrand charge transfer from mG10 to BrU5 within the four-base π-stacks in Z-DNA, ODN 1-3 samples in which the putative donor G10 residue was replaced with 8-methoxyguanine (moG) were prepared, since moG is known to trap cation radicals to yield Iz moieties in DNA. Photoirradiation of ODN 1-3 efficiently produced 5‘-d(CGC)rGd(UGCG)-3‘ together with formation of 5‘-d(CIzCACmGCG)-3‘. These results clearly indicate that the interstrand charge transfer from mG10 to BrU5 initiates the photoreaction. In clear contrast, other replacements of G with moG did not enhance the photoreactivity. The present study revealed the presence of unique four-base π-stacks in Z-DNA and photoirradition of BrU in Z-DNA causes efficient electron transfer from G within this cluster

C–C base pairs (left panel) and schematic structures of the i-motif topology from the C-rich complementary strand d(GCCGCCCAAAACCCCCCG) (middle and right panels)

<p><b>Copyright information:</b></p><p>Taken from "Formation of the G-quadruplex and i-motif structures in retinoblastoma susceptibility genes (Rb)"</p><p>Nucleic Acids Research 2006;34(3):949-954.</p><p>Published online 7 Feb 2006</p><p>PMCID:PMC1361614.</p><p>© The Author 2006. Published by Oxford University Press. All rights reserved</p

Biomolecule-Based Switching Devices that Respond Inversely to Thermal Stimuli

We demonstrate a molecular switch, on the basis of the characteristic properties of DNA and RNA, which indicates a completely inverted response to thermal stimuli using the transition between right- and left-handed helices. We designed a system using aminopurine (Ap), which can convert the π-stack information of the transition from right-handed to left-handed DNA (B−Z transition) and RNA (A−Z transition) into an output giving a fluorescent signal. These two biomolecular devices together serve as “right−left” or “off−on” switches. When the temperature is changed from low to high, the RNA device changes from the off to on signal; however, the DNA device changes from on to off. The response of these RNA and DNA based devices against thermal stimulus was completely reversible

Similarities and Differences between RNA and DNA Double-Helical Structures in Circular Dichroism Spectroscopy: A SAC–CI Study

The helical structures of DNA and RNA are investigated experimentally using circular dichroism (CD) spectroscopy. The signs and the shapes of the CD spectra are much different between the right- and left-handed structures as well as between DNA and RNA. The main difference lies in the sign at around 295 nm of the CD spectra: it is positive for the right-handed B-DNA and the left-handed Z-RNA but is negative for the left-handed Z-DNA and the right-handed A-RNA. We calculated the SAC–CI CD spectra of DNA and RNA using the tetramer models, which include both hydrogen-bonding and stacking interactions that are important in both DNA and RNA. The SAC–CI results reproduced the features at around 295 nm of the experimental CD spectra of each DNA and RNA, and elucidated that the strong stacking interaction between the two base pairs is the origin of the negative peaks at 295 nm of the CD spectra for both DNA and RNA. On the basis of these facts, we discuss the similarities and differences between RNA and DNA double-helical structures in the CD spectroscopy based on the ChiraSac methodology

Helical Structure and Circular Dichroism Spectra of DNA: A Theoretical Study

The helical structure is experimentally determined by circular dichroism (CD) spectra. The sign and shape of the CD spectra are different between B-DNA with a right-handed double-helical structure and Z-DNA with a left-handed double-helical structure. In particular, the sign at around 295 nm in CD spectra is positive for B-DNA, which is opposite to that of Z-DNA. However, it is difficult to determine the helical structure from the UV absorption spectra. Three important factors that affect the CD spectra of DNA are (1) the conformation of dG monomer, (2) the hydrogen-bonding interaction between two helices, and (3) the stacking interaction between nucleic acid bases. We calculated the CD spectra of (1) the dG monomer at different conformations, (2) the composite of dG and dC monomers, (3) two dimer models that simulate separately the hydrogen-bonding interaction and the stacking interaction, and (4) the tetramer model that includes both hydrogen-bonding and stacking interactions simultaneously. The helical structure of DNA can be clarified by a comparison of the experimental and SAC-CI theoretical CD spectra of DNA and that the sign at around 295 nm of the CD spectra of Z-DNA reflects from the strong stacking interaction characteristic of its helical structure

Photoreaction at 5‘-(G/C)AA^BrUT-3‘ Sequence in Duplex DNA: Efficent Generation of Uracil-5-yl Radical by Charge Transfer

The photoreactivities of 5-halouracil-containing DNA have widely been used for analysis of protein−DNA interactions and have recently been used for probing charge-transfer processes along DNA. Despite such practical usefulness, the detailed mechanisms of the photochemistry of 5-halouracil-containing DNA are not well understood. We recently discovered that photoirradiation of BrU-substituted DNA efficiently produced 2‘-deoxyribonolactone at 5‘-(G/C)AABrUBrU-3‘ and 5‘-(G/C)ABrUBrU-3‘ sequences in duplex DNA. Using synthetic oligonucleotides, we found that similar photoreactivities were maintained at the 5‘-(G/C)AABrUT-3‘ sequence, providing ribonolactone as a major product with concomitant release of adenine base. In this paper, the photoreactivities of various oligonucleotides possessing the 5‘-BrUT-3‘ sequence were examined to elucidate the essential factors of this photoreaction. HPLC product analysis indicated that the yield of 2‘-deoxyribonolactone largely depends on the ionization potential of the purine derivatives located 5‘-upstream of 5‘-BrUT-3‘, as well as the electron-donating ability of their pairing cytosine derivatives. Oligonucleotides that possess G in the complementary strand provided the ribonolactone with almost the same efficiency. These results clearly suggest that the photoinduced charge transfer from the G-5‘ upstream of 5‘-BrUT-3‘ sequence, in the same strand and the complementary strand, initiates the reaction. To examine the role of intervening A/T base pair(s) between the G/C and the 5‘-BrUT-3‘ sequence, the photoreactivities of a series of oligonucleotides with different numbers of intervening A/T base pairs were examined. The results revealed that the hotspot sequence consists of the electron-donating G/C base pair, the 5‘-BrUT-3‘ sequence as an acceptor, and an appropriate number of A/T base pairs as a bridge for the charge-transfer process

Base Pair Recognition of the Stereochemically α-Substituted γ-Turn of Pyrrole/Imidazole Hairpin Polyamides

Recognition of the sequences 5‘-NGCACA-3‘ (N = T, A, C, G) by pyrrole/imidazole polyamides with (R/S)-α-hydroxyl/α-amino-substituted γ-aminobutyric acid as a γ-turn was investigated. Four novel polyamides, 2, 3, 4, and 5, including (R)-α-hydroxyl-γ-aminobutyric acid (γRO), (S)-α-hydroxyl-γ-aminobutyric acid (γSO), (R)-α,γ-diaminobutyric acid (γRN), and (S)-α,γ-diaminobutyric acid (γSN) residues, respectively, were synthesized, and their binding affinity to T·A, A·T, G·C, and C·G base pairs at turn position was studied by the surface plasmon resonance (SPR) technique. SPR data revealed that polyamide 3, AcImβImPy-γSO-ImPyβPy-β-Dp, with a γSO turn, possesses a marked binding preference for T·A over A·T with a 25-fold increase in specificity, despite low binding affinity relative to 2, with a γRO turn. Similarly, AcImβImPy-γSN-ImPyβPy-β-Dp (5), with a γSN-turn, gives rise to a 8.7-fold increase in specificity for T·A over A·T. Computer-assisted molecular modeling suggests that 3 binds more deeply in the minor groove of the T·A base pair relative to the A·T base pair, allowing hydrogen bonding to O2 of the thymine at the turn position, which explains the SPR results. These results suggest that γSO and γSN may function as T-recognition units at the turn position, as well as a γ-turn in the discrimination of polyamides

The Distance Between Donor and Acceptor Affects the Proportion of C1′ and C2′ Oxidation Products of DNA in a ^BrU-Containing Excess Electron Transfer System

We have investigated the products of BrU in excess electron transfer and have demonstrated that in DNA the proportion of products changes with the distance between the donor and acceptor. On the basis of a labeling experiment using H218O, we have shown that hole migration from Py•+ formed after charge separation is involved in the reaction