Mouse telomeric DNA sequence, Tel3.5: 5′-AGGG(T TAGGG)3-3′, has the ability to form antiparallel tetraplex structure in the presence of Na+. We examined the interaction between the antiparallel tetraplex structure of Tel3.5 and each of two single-stranded telomeric DNA-binding domains of mouse telomere binding protein Pot1, mPot1OB1 and mPot1OB2. The antiparallel tetraplex of...
Fission yeast telomeric DNA sequence, SP4G4: 5′-(GGGGTTAC)4-3′ has been reported to form the antiparallel tetraplex in the presence of K+. We examined the structural properties of budding yeast telomeric DNA sequences, SCTELG4: 5′-(TGGGTGT G)4-3′ and SCTELGG4: 5′-(TGGGTGTGG)4-3′, in the presence of K+. The major conformation of SCTELG4 and SCTELGG4 was a parallel tetraplex DNA...
We have previously demonstrated that heme, iron(III)-protoporphyrin IX complex, and a parallel-quadruplex DNA assembled from d(TTAGGG) form a stable coordination complex called “heme-DNA complex”. The heme-DNA complex exhibits a variety of spectroscopic characteristics remarkably similar to those of met-form of myoglobin, oxygen-binding hemoprotein, reflecting that the heme...
We designed and synthesized DNA oligonucleotides that were able to fold into intramolecular DNA G-quadruplexes with different number of G-quartet planes and thymines in the each loop region [GmTn: m indicates the number of G-quartet planes (2 ≤ m ≤ 4), and n indicates the number of thymines in the each loop region (2 ≤ n ≤ 4)]. Effects of molecular crowding on structure of G...
We examined the structural properties of budding yeast telomeric DNA sequences, SCTELG4: 5′-(TGGG TGTG)4-3′ and SCTELGG4: 5′-(TGGGTGTGG)4-3′, in the presence of Na+ or K+. The conformation of SCTELG4 with Na+ was a mixture of parallel tetraplex DNA and unstructured single-stranded DNA. On the other hand, the conformation of SCTELGG4 with Na+ was a mixture of parallel and...
Telomestatin (TMS: 1) is as a potent and selective telomeric G-quadruplex binder. Two molecules of TMS were suggested to be intercalated to one telomeric G-quadruplex according to docking study. In this paper, we designed and synthesized hexaoxazole TMS derivative (6OTD) dimer, and evaluated its G-quadruplex stabilizing ability.
Nucleotide folding accompanies cation binding that shields the electronegative potential of phosphate groups, and metal ions in the condensation layer predominantly associate diffusely with base-paired nucleotides. Although metal ions bound at specific sites have been well studied, information of diffusely bound cations, that usually have a weak binding affinity than those...
Endogenous and environmental genotoxic agents produce DNA damage and induce cell death and mutations. The repair mechanisms of base lesions and single and double strand breaks have been well characterized in both prokaryotic and eukaryotic cells. However, the molecular pathways that repair or tolerate DNA-protein crosslinks (DPCs) remains to be largely elucidated. In this study...
To assess the involvement of specialized DNA polymerases in the mutagenesis induced by an oxidized form of dGTP, 8-hydroxy-2′-deoxyguanosine 5′-triphosphate (8-OH-dGTP, 7,8-dihydro-8-oxo-2′-deoxyguanosine 5′-triphosphate), shuttle plasmid DNA containing the supF gene and 8-OH-dGTP were introduced into human 293T cells in which specialized DNA polymerases were knocked-down by...
The (6–4) photoproduct, which is one of the major UV-induced DNA lesions formed at bipyrimidine sites, causes carcinogenesis at high frequency. The (6–4) photolyases restore the (6–4) photoproducts to their intact bases in a light-dependent manner, but its overall repair mechanism remains obscure. To investigate the light-dependent conversion of the (6–4) photoproduct, we...
8-Oxoguanine is the typical oxidative product, but 8-oxoguanine is further oxidized by several oxidizing agents. Here, we investigated the oxidation of 2′-deoxy-8-oxoguanosine with aqueous iodine.
Bisulfite modification is a principal tool for analyzing DNA methylation, the methyl substitution at position 5 of cytosine residues. Hypermethylation is known to cause silencing of genes, which may result in cell function failures. DNA methylation analysis is therefore a focus of attention in various fields of biological sciences, including even clinical practices for treatment...
The synthesis of DNA oligomer containing N4-hydroxy-5,6-dihydrocytosine-6-sulfonate by the simultaneous addition of bisulfite and hydroxylamine under mild conditions is reported. To the best of our knowledge, the reaction of the oxime into the ketone, N4-hydroxy-5,6-dihydrocytosine-6-sulfonate into 5,6-dihydrouracil-6-sulfonate or uracil has not been reported. Moreover, this...
The endogenous mutagenic/carcinogenic 9- (4′-aminophenyl) -9H- pyrido [3,4-b] indole (aminophenylnorharman, APNH) is formed from norharman and aniline in the presence of cytochrome P-450s. The major APNH-DNA adduct has been reported to be 2′-deoxyguanosin-8-yl-aminophenylnorhaman (dG-C8-APNH). In addition, demonstrated formation of APNH-RNA adduct and conducted a structural...
Photoirradiation and subsequent hot piperidine treatment of the duplex consisting of 5-methylcytosine (mC)-containing DNA and 9,10-anthraquinone (AQ)-tethered complementary oligodeoxynucleotide led to selective oxidative strand cleavage at the target mC site, whereas no strand cleavage was observed for the duplex containing normal cytosine instead of mC. Incorporation of an AQ...
We investigated the efficiency of osmium complex formation at 5-methylcytosine in mismatched DNA duplexes. Osmium complexation was not observed in fully matched duplexes, whereas the complexation site and efficiency in mismatched duplexes depended on the 5′-neighboring base of the 5-methylcytosine. In particular, when the base adjacent to the 5′ side of the mismatched base pair...
DNA duplexes containing diaminostilbene (DAS) as a photoinduced electron donor were synthesized to investigate mechanisms of electron injection into DNA and the succeeding electron transfer in the duplexes. DAS-Capped hairpin DNA showed a high structural stability thereby attains large interaction between DAS and the terminal base pair. DAS-Tethered DNA by a single linker at the...
We describe a selective and sensitive single-nucleotide polymorphism (SNP) typing of genes from rice cultivars by using DNA photoligation. This SNP typing method facilitates qualitative determination of genes from indica and japonica rice, and showed a high degree of single nucleotide specificity.
We describe a novel reversible interstrand photocrosslinking reaction of RNA. In this system, a modified oligodeoxynucleotide (ODN) containing 3-cyanovinylcarbazole nucleoside (CNVK) reacts by photoirradiation at 366 nm for 1 s with pyrimidine residue of a complementary template RNA to yield a crosslinked product in 94% yield.
We have successfully developed a new method for photoregulation of G-quadruplex formation using cis-trans photoisomerization of the photochromic nucleobase 8FVG. Our photo-controllable quadruplexes can be switched between a very stable quadruplex state and a non-structured state in a straightforward and reversible fashion. We also demonstrated reversibly control binding of a G...
We synthesized C8-vinylpyrene-substituted 2′-deoxyguanosine VPyG and studied the photoinduced reversible E–Z isomerization. When E-isomer was irradiated with visible light (>420 nm), E- to Z-isomerization took place very rapidly, while upon irradiation with UV-light (∼365 nm), Z-isomer was converted to E-isomer. When Z-isomer was illuminated with 365– 400 nm light, no...
A novel visible light sensitive azobenzene (AZO) was synthesized and introduced into bis-peptide nucleic acid (bis-PNA), which consists of two homopyrimidine PNA strands, as a linker. Visible light irradiation of the bis-PNA-AZO conjugate induced photoisomerization of the azobenzene moiety from trans to cis. The cis-form of bis-PNA-AZO displaced the complementary duplex DNA more...
A stable double helix involving alternating base pairs and azobenzene moieties was constructed. In this supramolecule, base pairs and azobenzenes are lined up one by one to form an interstrand-wedged motif: each base pair is sandwiched with two azobenzenes, and each azobenzene intercalates between two base pairs. This motif was formed by the hybridization of two modified DNA...
We designed and synthesized light-responsive BNA (bridged nucleic acid), which has a photolabile group at the bridged structure. Light-Responsive BNA can change its structure by a two stages process: photoirradiation followed by nucleophilic treatment. In oligonucleotides containing light-responsive BNA moieties, binding affinity with complementary single-stranded RNA was lost...
The C4′-oxidized abasic site (1) is one of the oxidatively damaged DNA lesions induced by antitumor bleomycins. The reactivity of 1 with amine under neutral conditions giving lactam 2 and its structural similarity to unmodified DNA suggested the possibility that ODN containing 1 could react with proteins which interact with DNA at lysine residue. In order to provide nucleic acid...