Synapsable quadruplexmediated fibers nanoscale research. As shown in the figure below left, in the hoogsteen bp scheme, adenine uses its n7 acceptor and n6 donor atoms at the major groove edge to form two hbonds with the n3 donor and o4 acceptor atoms from uracil, respectively. The guanidinium group of arg35 is stabilized by hydrogen bonds to g25 and to the phosphate backbone, and is positioned to stack with c22. The spacer nucleotide, in this sequence g24, has sufficient flexibility to allow u23 to flip into the major groove and form a hoogsteen base pair with a26, which is base paired with u9. Manleya,2, yongsheng shic, thomas walzb,2, and liang tonga,2 adepartment of biological sciences, columbia university, new york, ny 10027. Introduction of potassium ions induces the guaninerich tracts in the duplex precursors to hoogsteen base pair, creating a dna element called a guanine quartet. In a hoogsteen base pair, the nucleotide base a is flipped in comparison to the watsoncrick pairing. The transitions between wc and hg may play a role in recognition and replication, but are dif. D detailed view of the base pairs surrounding u177.
It has been discovered in 1957 that a homopyrimidine dna strand triplex forming oligonucleotide, tfo can bind to a homopurinehomopyrimide dna duplex in the major groove by forming hoogsteen base pairs with the homopurine strand. Structure of the dna duplex dattaat2 with hoogsteen. Sequencespecific alkylation and cleavage of dna mediated by. These protons and 31p, suffers from relatively small chemical shift dispersions. The observation of hoogsteen base pairs in dna duplexes specifically bound to transcription factors and in damaged dna sites implies that the dna double helix intrinsically codes for excited state hoogsteen base pairs as a means of expanding its structural complexity beyond that which can be achieved based on watsoncrick basepairing. Nucleic acids transiently morph into alternative conformations that can be difficult to characterize at the atomic level by conventional methods because they exist for too little time and in too little abundance. Database utilities provides structural references in the form of base pair annotation for dna, rna, and some proteins contains search engine to find data on many dna and rna strcuctures depicts these structures through systematic design based on biological data includes innovative methods of examining dna structures.
A molecular dynamics study of the bisintercalation complexes. While this may not look really different, keep in mind that nucleotide bases are connected to the dna backbone. Errorprone replication of oxidatively damaged dna by a. Structure of an rna aptamer that can inhibit hiv1 by. Thermodynamic stability of hoogsteen and watsoncrick base. Apr 16, 2018 modulation of hoogsteen dynamics at binding interfaces may be a general phenomenon with important implications for dnaligand and dnaprotein recognition. Pnas bind to ribonucleic acid rna duplexes via complementary hoogsteen hydrogen bonding to form pnarna2 triplexes. Noncanonical base pairing schemes reversed wc hoogsteen, reversed hoogsteen 8 wobble, guanine antiadenine. Furthermore, the predicted helical stability was comparable to that of the corresponding antiparallel bdna structure. In pkdu, u103 forms a hoogsteen base pair with g178. Errorprone replication of oxidatively damaged dna by a high.
Transient hoogsteen base pairs in canonical duplex dna article pdf available in nature 4707335. New insights into hoogsteen base pairs in dna duplexes. A base pairs, because the val29 residue of tbp precludes a g. A single nucleotide change in a core promoter is involved in. Rather than observing a watsoncrick wc bp, a unique pairing geometry was observed in which the adenine base was flipped 180 to form a unique set of hydrogen bonds hbonds figure. Sequencespecific alkylation and cleavage of dna mediated. In this manner, two nucleobases, one on each strand, can be held together by hydrogen bonds in the major groove. Why are hoogsteen base pairs energetically disfavored in a. May 10, 2015 however, dna can also assume the hoogsteen conformation, where the purine is flipped which changes the hydrogen bonds that are possible between the bases. Yet, no individuals are asserted to be instances of hoogsteen edges, rather since mcannotate generates assertions at the subedge level, it is also necessary to ask for any parts of the edges.
However, dna can also assume the hoogsteen conformation, where the purine is flipped which changes the hydrogen bonds that are possible between the bases. By continuing to use our website, you are agreeing to our use of cookies. All structured data from the file and property namespaces is available under the creative commons cc0 license. In this study, we describe the correction of singlepoint mutations in mammalian cells by repairpolypurine reverse hoogsteen hairpins repairpprhs. Hoogsteen hg base pairs bps were discovered in 1959 when karst hoogsteen used single crystal xray crystallography to visualize the pairing between 1methylthymine and 9methyladenine. Widespread transient hoogsteen basepairs in canonical duplex. A stable intermediate dimeric grich form as a precursor of tetrameric gquadruplex structures has been detected via malditof spectrometry.
None of the observed stabilizing contacts are out of the ordinary. Threedimensional structures of bulgecontaining dna. Transient hoogsteen base pairs in canonical duplex dna. Molecular dynamics simulation offered detailed insights at the atomic level, assigning reverse watsoncrick gg base pairing not hoogsteen in the grich dimer. The hoogsteen base pair, consisting of a syn adenine base paired with an anti thymine base, is found in the 2. Chemical and enzymatic footprinting of quinoxaline.
It is shown that this antiparallelstranded hoogsteen base paired structure can be maintained under varying conditions, balancing the decrease in ph with an increased salt concentration. In the purine motif, ggc, aat, and tat triplets result from the formation of reverse hoogsteen hydrogen bonds in the major groove of dna between an antiparallel purinerich third strand and. The loopedout base intercalates into the stackedin bulge site of a symmetrically related duplex. Using this model at pair system, we gain the first experimental insights into whether edpt is active in uvexcited at, and directly compare and contrast the findings from these results with our previous studies on gc. Information on the backbone structure can be obtained from a limited number of nuclei, namely, h3. Structure of 2,4diaminopyrimidine theobromine alternate. The dg x c reverse watsoncrick basepair was estimated to be more stable by approximately 1. Dec 01, 2002 the hoogsteen base pair, consisting of a syn adenine base paired with an anti thymine base, is found in the 2. In contrast, adopting a less conventional syn conformation and thus forming a stable hoogsteen base. If a base in a template strand exists in its rare tautomeric form misincorporation in the daughter strand can result. The hoogsteen base pair appears to be stabilized by an extra interbase pair hydrogen bond and base stacking within the dna, as well as by contacts made by one of the nonspecifically bound mat.
This file is licensed under the creative commons attributionshare alike 4. Rather than observing a watsoncrick wc bp, a unique pairing geometry was observed in which the adenine base was flipped 180 to form a unique set of. Probing transient hoogsteen hydrogen bonds in canonical. Thus, the base pair isostericity nicely explains the covariation pattern for these base pairs. The au or at hoogsteen pair is a wellknown type of base pair bp, named after the scientist who discovered it. Dot bracket notation for rna and dna nanostructures. A single nucleotide change in a core promoter is involved.
A molecular dynamics study of the bisintercalation. In this study, modifications were made to chemically synthesize the pna sequences incorporated with q, modified q and 2thio uracil monomers to target the inverted watsoncrick cg base pair present in rna hairpins. Evidence for hoogsteen gc base pairs in the protoninduced. Towards the sequenceselective recognition of double. Crowding promotes the switch from hairpin to pseudoknot. Correction of the aprt gene using repairpolypurine reverse. These molecules consist of 1 a pprh hairpin core that binds to a polypyrimidine target sequence in the doublestranded dna dsdna, producing a triplex structure, and 2 an extension sequence homologous to the dna sequence. Thus, it is not clear whether the second tatabox octamer of the cyp9m10 promoter tata2 in fig. The dna double helix is usually stabilized by watsoncrick wc hydrogen bonds between the bases. In contrast, the fifth nucleotide has a more conserved prevalence of a. Jun 22, 2010 the individual must be an instance of the nucleotide base pair class, but this base pair must further be specified by a hoogsteen edge.
A hoogsteen base pair is a variation of basepairing in nucleic acids such as the at pair. Molecular basis for the recognition of the human aauaaa polyadenylation signal yadong suna,1, yixiao zhangb,1, keith hamiltona, james l. A reversed hoogsteen basepair that stacks between the surrounding base. Dec 20, 2011 in pkdu, u103 forms a hoogsteen base pair with g178. The grich strands of most eukaryotic telomeres are capable of forming highly folded structures in vitro, mediated, in part, through hoogsteen gg base pairing.
Hoogsteen bps have been reported in a handful of x. U100b 9a174 u115, u101b 9a175 u114, u102b 9a176 u1, a172o 4g98dc116, a171o 4u97d a117, and a1690 4g118dc96 see ref 9 for. Antiparallel and parallel combinations of adenine a and uracil u base pair faces. The individual must be an instance of the nucleotide base pair class, but this base pair must further be specified by a hoogsteen edge. A key element of antitumor drug design is an understanding of how naturally occurring antitumor antibiotics recognize and bind to dna, the major means by which many of t. This page was last edited on 24 november 2018, at 07. The area of the squares is proportional to the binding probability 172 i. Nmr studies of the free dna show no evidence of hoogsteen base pair. In the final structure, the central six guanines are involved in creating the guanine quartets 24, and four duplex tails, two at each end, project from the quadruplex core. Specificity of dna triple helix formation analyzed by a. Indeed, incorporation of a 2omethyl nucleotide into an antisense oligo resulting in a 2omethyl rnadna chimeric, lead to a. The hoogsteen base pairs geometry can be achieved by purine rotation around the glycosidic bond. Widespread transient hoogsteen basepairs in canonical.
New insights into hoogsteen base pairs in dna duplexes from a. The ability of pol to push the template purine a or g residue into a syn conformation and to form an hoogsteen base pair with the incoming t or c, respectively, enables it to insert nucleotides. One nucleotide base is connected to one helix, and the other is connected to the other helix. Stacked and tshaped structures ofthe 24dap tb alternate base pair. Modulation of hoogsteen dynamics on dna recognition. A historical account of hoogsteen basepairs in duplex dna. Realspace evidence of watsoncrick and hoogsteen adenine. Files are available under licenses specified on their description page. These molecules consist of 1 a pprh hairpin core that binds to a polypyrimidine target sequence in the doublestranded dna dsdna, producing a triplex structure, and 2 an extension sequence homologous to the dna sequence to be repaired but. H trans base pair, although less stable and nonisosteric with the above pairs leontis et al. Pdf transient hoogsteen base pairs in canonical duplex dna. We recently reported evidence for transient hoogsteen hg base pairs in canonical bdna based on nmr carbon relaxation dispersion. Database utilities provides structural references in the form of base pair annotation for dna, rna, and some proteins contains search engine to find data on many dna and rna strcuctures depicts these structures through systematic design based on biological data includes innovative methods of.
What is the difference between watsoncrick and hoogsteen. Interaction energies in kcalmol of the examined systems avtza avqzb cbsc. Binding of dsrnas by pnas containing q, modified q and 2. The nucleotides are in cpk colors, except that u177 is colored magenta. Occasionally a different type of structure is found. Structure of 2,4diaminopyrimidine theobromine alternate base. Dec 27, 2019 hoogsteen and watsoncrick base pairings. Chemical structures for watsoncrick and hoogsteen base pairs. Cpsf160 functions as an essential scaffold and preorganizes cpsf30 and wdr33 for highaffinity binding to aauaaa. From 1h nmr studies the recognition of pyrimidinepurine base pairs by d3 was found to be the result of intercalation by d3 at the 3 site of the target base pair. The hydrogen bonding behavior of a 2omethyl rnarna base pair is closer to that of an rnarna base pair than a dnarna base pair. Hoogsteentypemotifsareexcludedin this case because the 7methyl group blocks the necessary hydrogen bonding site. Such a study may provide a model system to unravel some biologically relevant issues in rna duplex, e.
Hoogsteen base pairs form through concurrent rotation of the purine base about the glycosidic bond from an anti to a syn conformation and constriction of the c1c1 distance across the base pair. Molecular basis for the recognition of the human aauaaa. Consequently, the presence of 2omethyl nucleotides improves duplex stability. Our findings demonstrate that the type of dna base pair is critical for the interaction between dna and histones. Our findings demonstrate that the type of dna base pair is critical for. Hoogsteen gg base pairing is dispensable for telomere. Correction of the aprt gene using repairpolypurine. At wc base pair, solvated in chloroform solution, which eliminates formation of undesired hoogsteentype structures. The dg x c reverse watsoncrick base pair was estimated to be more stable by approximately 1.
The ability of most telomeres to form these structures has led to the suggestion that they play an important role in telomere addition. The hoogsteen base pairing scheme mediates sequence specific recognition of the double stranded dna by the tfo where an at. Hoogsteen base pairs form through concurrent rotation of the purine base about the glycosidic bond from an anti to a syn conformation and constriction of. Basic principles of forensic molecular biology and genetics. Apr 20, 2015 hoogsteen hg base pairs bps were discovered in 1959 when karst hoogsteen used single crystal xray crystallography to visualize the pairing between 1methylthymine and 9methyladenine. While purine dna bases adenine and guanine tend to favor the anti conformation in watson and crick base pairing, the rotation in hoogsteen base pairing puts the purine in the syn. Atomistic insight into the kinetic pathways for watson.
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