Atomistic insight into the kinetic pathways for watson. Free energy landscape and transition pathways from watson. Another form of base pairing is known as hoogsteen base pairs, but in this conformation the g. Kimsey1, bharathwaj sathyamoorthy1, shan yang2, jane s. Pergamon tetrahedron letters 39 1998 52215224 tetrahedron leiters stabilization of hoogsteen base pairing by introduction of nh2 group at the c8 position of adenine kiyohiko kawai, and isao saito department of synthetic and biological chemistry, graduate school of engineering, kyoto university, kyoto 6068501, japan. They are different geometries of base pairings between at and gc bonds.
Here the authors describe the influence of echinomycin and. C base pair is stable only under slightly acidic conditions ph 45, due to the necessary protonation of cytosine. Changwon yang, eunae kim, youngshang pak, free energy landscape and transition pathways from watsoncrick to hoogsteen base pairing in free duplex dna, nucleic acids research, volume 43, issue 16, 18 september 2015. More than two decades ensued without experimental proof for at watsoncrick base. In an at hoogsteen base pair, two hydrogen bonds form between the hoogsteen edge of adenine n7 and n6 and the wc edge of thymine n3. Our findings also expand the current understanding of proteindna recognition and establish the structural and chemical properties of hoogsteen base pairs as the basis for a novel mode of sequence readout. All structured data from the file and property namespaces is available under the creative commons cc0 license. A hoogsteen base pair is a variation of base pairing in nucleic acids such as the at pair. Probing detailed transition mechanism from watsoncrick wc to hg base pair bp formation in duplex. Hoogsteen base pair definition by babylons free dictionary. Hoogsteen base pairs proximal and distal to echinomycin. When the base pairing probability matrix is calculated by symbols, are used for bases that are essentially unpaired, weakly.
Dot bracket notation for rna and dna nanostructures. In this manner, two nucleobases, one on each strand, can be held together by hydrogen bonds in the major groove. These are only examples of many alternative formsofbasepairingindna. Abstract hoogsteen dna base pairs bps are an alternative base. Xray crystallography and nmr relaxation experiments revealed the presence of hg base pair in naked dna duplex and proteindna complex but no hg base pair was observed in rna. Survey and summary new insights into hoogsteen base.
To finetune the stability of such base pairs and the selectivity toward different metal. Hoogsteen base pairs have been known for more than 40 years. Recent experiments have shown that hg pairing, in which the purine is upsidedown relative to the wc motif, makes up a nonnegligible fraction of dna at physiological conditions. In a normal watsoncrick pair, the two c1 atoms are equidistant at about 10. Hg base pairs and the consequent nucleotide incorporation. Soon after the model of dna was proposed 14 several attempts were made to demonstrate that watsoncrick pairing was favored by isolated bases. Free energy landscape and transition pathways from watsoncrick. Nucleic acid bases can also form hoogsteen hg base pairs in the major groove of a wc base paired dna duplex. Free energy landscape and transition pathways from watsoncrick to. Could you explain to me what the difference is betwe.
What is the difference between watsoncrick and hoogsteen. W trans pair interact with a third base to form a second planar base pair. Kima,n a department of chemistry, yeungnam university, daedong, gyeongsan city, gyeongbuk 712749, republic of korea b department of chemistry, kyungpook national. Watsoncrick to hoogsteen base pair transition simulations. A hoogsteen base pair applies the n7 position of the purine base as a hydrogen bond acceptor and c6 amino group as a donor, which bind the watsoncrick n3c4 face of the pyrimidine. Understanding hoogsteen hg base pairing is important because the underlying. The standard view of the genome is that the two dna strands are linked by watsoncrick base pairing. Pdf transient hoogsteen base pairs in canonical duplex dna.
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. Karst hoogsteen october 1, 1923 august 10, 2015 was a dutchborn american biochemist famous for noting a new base pairing form in dna, now called hoogsteen base pairs. Nmr studies of the free dna show no evidence of hoogsteen base pair formation, suggesting that protein binding favors the transition from a watsoncrick to a. Widespread transient hoogsteen base pairs in canonical. Free energy landscape and conformational kinetics of hoogsteen. There is now little doubt that hoogsteen basepairs exist in significant. The free energy and enthalpy of the wctohg transition were found to closely match. This hyperreactive segment may be an altered form of righthanded dna that is entirely hoogsteen base paired. Hoogsteen base pair an overview sciencedirect topics. The m6a methylation perturbs the hoogsteen pairing guided incorporation of an oxidized. By using nuclear magnetic resonance relaxation dispersion spectroscopy in concert with steered molecular dynamics simulations, we have observed transient sequencespecific excursions away from watsoncrick base pairing at ca and ta steps inside canonical duplex dna towards lowpopulated and shortlived at and gc hoogsteen base pairs.
Hoogsteen hg base pairing involves a 180 rotation of the purine base relative to watson. Survey and summary new insights into hoogsteen base pairs in dna duplexes from a structurebased survey huiqing zhou1, bradley j. Dot bracket notation for rna and dna nanostructures slides by reem mokhtar. We have presented tps simulations describing the transitions between the wellknown watsoncrick base pairing motif and the hoogsteen base pairing motif. Hoogsteen pairs have quite different properties from watsoncrick base pairs. Watsoncrick and hoogsteen are two different types of base pairing conformations that dna base pairs may assume. Identifying hoogsteen base pairs in dna duplexes remains challenging due to difficulties in resolving syn versus antipurine bases with x. These base pairing intercede in the watsoncrick base pairing, forging a base pair triplex. In a standard hoogsteen base pair the pyrimidine uses its watsoncrick surface to pair with the n1, c6, n7 side of the purine base. The base pairs use the n7 nitrogen atom as the accepter rather than the n1 as observed in watsoncrick base pairing. Free energy landscape and conformational kinetics of.
Pdf new insights into hoogsteen base pairs in dna duplexes. Pdf comparable stability of hoogsteen and watsoncrick. Crystal structure of an antiparallel dna fragment with. Free energy landscape and transition pathways from watsoncrick to hoogsteen base pairing in free duplex dna changwon yang1, eunae kim2 and youngshang pak1, 1department of chemistry and institute of functional materials, pusan national university, busan 609735, south korea and 2college of pharmacy, chosun university, gwangju 501759, south. Similarly, in s53, s33, s55, s stands for stacking and the two number stand for the face used by the first base and second base in the interaction respectively. Here we describe an nmr strategy for characterizing hoogsteen base pairs. Alhashimi1,3, 1department of biochemistry, duke university, durham, nc 27710, usa, 2department of biochemistry. Biochemical evidence for the requirement of hoogsteen base. The au or at hoogsteen pair is a wellknown type of base pair bp, named after the scientist who discovered it.
The center two ta pairs represent hoogsteen base pairs. However, the effects of molecular crowding on watson. Modulation of hoogsteen dynamics on dna recognition. Dna is found in a dynamic equilibrium between standard watsoncrick wc base pairs and nonstandard hoogsteen hg base pairs. Moreover, a 12 base pair segment of alternating at dna, which is 6 base pairs away from the nearest strong echinomycinbinding site, is also hyperreactive to diethyl pyrocarbonate in the presence of echinomycin. Such a study may provide a model system to unravel some biologically relevant issues in rna duplex, e. The m6a methylation perturbs the hoogsteen pairingguided. Thermodynamic stability of hoogsteen and watsoncrick base pairs in the presence of histone h3mimicking. A nature paper on spontaneous flipping of normal watsoncrick wc base pairs into hoogsteen hg base pairs in naked dna under most normal conditions1 produced the bombshell effect throughout the world community of nucleic acids biophysicists. New insights into hoogsteen base pairs in dna duplexes from a structurebased survey.
Free energy landscape and transition pathways from watsoncrick to hoogsteen base pairing in free duplex dna article pdf available in nucleic acids research 4316 august 2015 with 182 reads. A hoogsteen base pair is a variation of basepairing in nucleic acids such as the at pair. Reverse watsoncrick purinepurine base pairs biorxiv. In order to investigate directly and quantitatively the. Subtraction of free tbp from bound yields the spectrum of the bound dna. Our results suggest a mechanism relating spacer length to proteindna binding affinity. This page was last edited on 24 november 2018, at 07. Stabilization of hoogsteen base pairing by introduction of. Significance formation of unconventional hoogsteen hg base pairing is an important problem in dna biophysics owing to its key role in facilitating the binding of dna repairing enzymes, proteins and drugs to damaged dna. A historical account of hoogsteen basepairs in duplex dna. Also the angle of glycosidic bonds is larger in hoogsteen base pairs. Pdf free energy landscape and transition pathways from. A hoogsteen base pair applies the n7 position of the purine base as a hydrogen bond acceptor and c6 amino group as a donor, which bind the watsoncrick n3n4 face. Interestingly, only the dg,t and dg x c base pairs were observed in the heteroduplexes, suggesting that both the dg x t reverse wobble and dg x c reverse watsoncrick base pairs are more stable in this crystal environment than the dg x g reverse hoogsteen base pair.
View the article pdf and any associated supplements and figures for a period of 48 hours. Some deviations from this canonical pairing have been observed when dna is bound to a ligand. Files are available under licenses specified on their description page. Effects of deficient of the hoogsteen basepairs on the g. Characterizing watsoncrick versus hoogsteen base pairing. Comparable stability of hoogsteen and watsoncrick base pairs in ionic liquid choline dihydrogen phosphate article pdf available in scientific reports 4. Nmr studies of the free dna show no evidence of hoogsteen base pair formation, suggesting that protein binding favors the transition from a watson crick to a. Pdf hoogsteen hg base pairs bps provide an alternative pairing geometry to watsoncrick wc. T hoogsteen base pairs can form in duplex dna and play roles in recognition, damage repair, and replication. The watsoncrick base pairs have specific hydrogen bonds that form between the base pairs.
Molecular dynamics simulations of the homeodomaindna complex support a role for the nonspeci. Geometric nomenclature and classification of rna base pairs. Andricioaei duplexdnabeyondwhatcanbeachievedbywatsoncrickbasepairingalone. Transient hoogsteen base pairs in canonical duplex dna. Thermodynamic stability of hoogsteen and watsoncrick. It has been revealed recently that molecular crowding, which is one of the largest differences between in vivo and in vitro conditions, is a critical factor determining the structure, stability, and function of nucleic acids. Xray crystallography and nmr relaxation experiments revealed the presence of hg base pair in naked dna duplex and proteindna complex but no hg base pair. Hoogsteen gg base pairing is dispensable for telomere healing in yeast. Occasionally, an alternative pairing, the hoogsteen base pair, was suggested to account for particular cases of specificity 12.
Houghton hg base pairing plays a central role in the dna binding of proteins and small ligands. The bottom left structure shows a wobble gt base pair. Pdf a hoogsteen base pair embedded in undistorted bdna. Metalmediated hoogsteen type base pairs are useful for the construction of dna duplexes containing contiguous stretches of metal ions along the helical axis. There is now little doubt that hoogsteen base pairs exist in significant abundance in genomic dna where they can expand the structural and functional versatility of duplex dna beyond that which can be achieved based only on watsoncrick base pairing.