A reverse hoogsteen base pair involves flipping one of the bases 180 with respect to the other. Nmr investigation of hoogsteen base pairing in quinoxaline. Crick base pairing and not by hoogsteen base pairing based on the almost identical insertion efficiencies of a and 7deazaa, the latter of which lacks hbonding capability at n7. We have investigated the possible formation of a parallel dna structure involving hoogsteen hydrogen bonds by thermal denaturation, ftir spectroscopy and gelshift experiments.
Rates and populations were obtained using nmr relaxation dispersion methods as described previously. Possible base pairs for the modified nucleotide 1 deaza adenine are shown. Its presence in crystals of oligonucleotides bound to some antibiotics, and its possible existence in solution and within long dna fragments remains to be. Ligandinduced formation of hoogsteenpaired parallel dna. Bases of the two antiparallel strands form hoogsteen pairs, with adenines in the syn. Free energy landscape and conformational kinetics of. This paper now shows that naked dna itself can transiently adopt a hoogsteen basepairing arrangement. Abrescia, andrew thompson, tam huynhdinh, and juan a. Why are hoogsteen base pairs energetically disfavored in a. Recent nmr relaxation experiments revealed the transient presence of an alternative, hoogsteen base pairing pattern in naked dna duplexes and estimated its relative stability and lifetime. In stabilization of the gquadruplex, formation of a hoogsteen basepair between the guanine g bases is essential. Noncanonical base pairing occurs when nucleobases hydrogen bond, or base pair, to one another in schemes other than the standard watsoncrick base pairs which are adenine a thymine t in dna, adenine a uracil u in rna, and guanine g cytosine c in both dna and rna. Nmr relaxation dispersion studies indicate that in canonical duplex dna, watsoncrick base pairs bps exist in dynamic equilibrium with. Atomic structures of excited state at hoogsteen base pairs in.
Hoogsteen bps have been reported in a handful of x. The helical structure of dna is variable and depends on the sequence as well as the environment. C n 1methylated purines disrupt wc bps via steric clashes red dashes and loss of hydrogen bonding. Thus, incorporation of the flexible base stacking monomer of the present invention into an oligonucleotide allows the. Since gc base pairing is stronger than at this means that gc base pairs resist denaturation by heat more so than at base pairs. Distinct mechanisms of cissyn thymine dimer bypass by. Why are hoogsteen base pairs energetically disfavored in arna.
However, at any time, a nonnegligible fraction of base pairs exhibit a different interaction pattern, called hoogsteen hg where the purine base is rotated approximately 180o relative to its orientation in the wc pairing. Hoogsteen base pairs utilize the c6n7 face of the purine for hydrogen bonding with the watsoncrick n3c4 face of the pyrimidine hoogsteen, 1963. A and b show chemical drawings in a watsoncrick wc and b hoogsteen hg configuration. Resolving a role in normal biological processes and human diseases hoogsteen basepairing revisited. Note that the adenine base has now two hydrogenbond acceptor atoms n1 and n3 in the major groove side and none in the minor groove, whereas in the b form. The first evidence for hgtype basepairs in damaged dna was reported in the late 1980s in solution nmr studies by patel and coworkers showing that guanine adducts on the watsoncrick edge or the c8 positions strongly favor a syn base orientation. The base pairs use the n7 nitrogen atom as the accepter rather than the n1 as. All structured data from the file and property namespaces is available under the creative commons cc0 license.
Pdf hoogsteen base pairs within duplex dna typically are only observed in regions containing significant distortion or near sites of. The compounds induce a reorganization from a nonperfectly matched antiparallel. Jan 26, 2011 this paper now shows that naked dna itself can transiently adopt a hoogsteen base pairing arrangement. Files are available under licenses specified on their description page. Some deviations from this canonical pairing have been observed when dna is bound to a ligand. Pdf comparable stability of hoogsteen and watsoncrick base. Importance of the reverse hoogsteen base pair 5458. Genetic information is encoded in the dna double helix which, in its physiological milieu, is characterized by the iconical watsoncrick nucleobase pairing. In the adenine and thymine hoogsteen pairing, the nucleobases found on the two dna strands are bound together by hydrogen bonds, using the n7 and exocyclic amine of the. The importance of the watsoncrick complementary base pairing scheme has rather overshadowed alternative types of base pairs in dna. By contrast to a wc base pair where the complementary purine and pyrimidine bases are both in the anti configuration fig. Dnaat triplexes with hoogsteen base pairing are more. Do hoogsteen base pairs occur in dna trends in biochemical. In the canonical watsoncrick dna base pairing, adenine a forms a base pair with thymine t, and guanine g forms a base pair with cytosine c.
Pdf new insights into hoogsteen base pairs in dna duplexes. Comparable stability of hoogsteen and watsoncrick base pairs in ionic liquid choline dihydrogen phosphate article pdf available in scientific reports 4. 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. Triplehelical structures involve, in addition to the normal watsoncrick base pairing, the hoogsteen base pairing. However, molecular modeling shows that these purinepurine base pairs can very closely mimic the reverse hoogsteen base pair u. These base pairing intercede in the watsoncrick base pairing, forging a base pair triplex. An indolelinked c8deoxyguanosine nucleoside acts as a. The achiral, uncharged and rather flexible properties of the peptide backbone permit peptide nucleic acids more potential than oligonucleotides in application to antisence and antigenic reagents. A, b and zdna helix families david w ussery,danish technical university, lyngby, denmark there are three major families of dna helices. This indicates that the sequence dependent nature of hoogsteen base pairing is the same in tpa specific and cpg specific quinoxaline antibiotic dna complexes. The latter type of base pairing can be observed, however, using bulky groups attached to bases, which prevent watsoncrick base pairing l 11. Resolving a role in normal biological processes and human diseases ghosal, gargi.
Biochemical and biophysical research communications, 343 1. Crystal structure of an antiparallel dna fragment with hoogsteen base pairing nicola g. A hoogsteen base pair is a variation of basepairing in nucleic acids such as the at pair. Trans hoogsteensugar edge hse rna base pairs form one of the six families of rna base pairs that utilize the 2. Alternate hydrogen bonding patterns, such as the wobble base pair and hoogsteen base pair, also occur in particular, in rna giving rise to complex.
Resolving a role in normal biological processes and human diseases. Effects of deficient of the hoogsteen basepairs on the g. One of these alternative base pairings, which is known as hoogsteen pairing, is now receiving attention. Path sampling simulations of the mechanisms and rates of. This page was last edited on 24 november 2018, at 07. A characteristic feature of hoogsteen base pairing is that the n7 position of the purine is basepaired, altering the chemical reactivity of this position. An indolelinked c8deoxyguanosine nucleoside acts as a fluorescent reporter of watsoncrick versus hoogsteen base pairing katherine m. An important nonwatsoncrick basepairing pattern was first described by karst hoogsteen in 1963 and bears his name. For a long time since the discovery of an alternative type of hydrogen bonding between adenine and thymidine, termed hoogsteen basepairing, its biological role remained elusive. Doublehelical polynucleo tides usually adopt watsoncrick base pairing rather than hoogsteen pairing. This file is licensed under the creative commons attributionshare alike 4. Biochemical evidence for the requirement of hoogsteen base pairing for replication by human dna polymerase. Furthermore, insertion of a opposite both ts of the dimer appears to be mediated by watson. Jul 26, 2005 because of the near geometric identity of watsoncrick wc gc and at base pairs, a given dna polymerase forms the four possible correct base pairs with nearly identical catalytic efficiencies.
B wc bps in bdna exist in dynamic equilibrium with hg bps. Recent experiments provide compelling evidence that hoogsteen base pairs manifest in a gamut of nuclear processes encompassing gene expression, replication, recombination, and telomere. Transient hoogsteen base pairs in canonical duplex dna. This excited state base pairing provides a means to expand the chemistry and structure of dna. A historical account of hoogsteen basepairs in duplex dna. Nucleic acid structure furman student created bioorganic.
Its presence in crystals of oligonucleotides bound to some antibiotics, and its possible existence in solution and within. Parallelstranded duplex with a hoogsteen base pair was reported in homopurinehomopyrimidine strands9 and 33 and 55 linked. These arrangements involve atoms n6 and n7 of adenine rather than the n1. A cocrystal structure obtained from an equimolar mixture of 6isopropyluracil and adenine shows the formation of a tri base pairing, where one molecule of free adenine is adhered to two molecules of the free pyrimidine nucleobase, involving. Based upon these observations, a similar mechanism involving hoogsteen base pairing of the 5. Here we describe an nmr strategy for characterizing. Dec 01, 2002 the hoogsteen base pair geometry, which was first observed in crystal structures of monomeric adenine and thymine base derivatives, is characterized by hydrogen bonds between the side of the purine base that faces the major groove and the watsoncrick base pairing face of the pyrimidine. As a guaninecytosine gc base pair has no potential to form a hoogsteen base pair at physiological ph, hoogsteen base pairing is. In addition, temperaturedependent uv spectroscopy shows an increase in melting temperature for the. Feb 24, 2011 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 base pairing. B conformation with watsoncrick base pairing has been found. Pdf comparable stability of hoogsteen and watsoncrick. More than two decades ensued without experimental proof for at watsoncrick base.
Effects of deficient of the hoogsteen base pairs on the g. Biochemical evidence for the requirement of hoogsteen base. The rules of base pairing explain the phenomenon that whatever the amount of adenine a in the dna of an organism, the amount of thymine t is the same called. A structural comparison of bform dna and aform rna. Stabilization of hoogsteen base pairing by introduction of nh 2. Parallelstranded dna with hoogsteen base pairing stabilized.
Hoogsteen base pairing cationic porphyrin circular dichroism abstract background. This type of triplebase bonding is of biological importance. In stabilization of the gquadruplex, formation of a hoogsteen basepair between the guanine g bases is. An important aspect of the oligonucleotides of the present invention is that they are capable of watsoncrick base pairing and hoogsteen base pairing and reverse hoogsteen base pairing.
While evidence is emerging that the hoogsteen conformation could be a thermodynamically accessible conformation of the dna. Molecular dynamics simulations of novel hoogsteen like bases that recognize the ta base pair by dna triplex formation. Unlimited viewing of the articlechapter pdf and any associated supplements and figures. Dna supercoiling nucleic acid double helix dna free. The conversion from wc to hg alters the conformation of dna, and may play a role in several. These were studied with respect to their thermal stability as well as of the base pairing mode watsoncrick vs. Jp5284084b2 stable and selective formation of hoogsteen. The synthesis of the corresponding phosphoramidite building block 7 was analogous to that for the natural riboseries 27, and started from the bicyclic sugar analog 1 and the nitrobase 2 fig. Thus, incorporation of the flexible base stacking monomer of the present invention into an oligonucleotide allows the oligonucleotide to form a triplex. Xray crystallography and nmr relaxation experiments revealed the presence of hg base pair in naked dna duplex and protein. In stabilization of the gquadruplex, formation of a hoogsteen base pair between the guanine g bases is essential. Hoogsteen dna base pairs bps are an alternative base pairing to canonical watsoncrick bps and are thought to play important biochemical roles.
This change consequently alters the width of the dnahelix, the sizes of minor and major groove and biophysical. Shingho department of biochemistry and biophysics, als 2011 oregon state university corvallis, or 97331, usa we have solved the structures of. Transient hoogsteen base pairs in canonical duplex dna nature. Recent findings showed that nonharmonic dnananostructures are formed by hoogsteen hg dinucleotides in vivo. Hoogsteen base pair an overview sciencedirect topics. 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. The three hbonds in gc base pairing have an overall strength of 6 kcalmol in comparison to the 4 kcalmol strength of at pairing. The synthesis of the corresponding phosphoramidite building block 7 was analogous to that for the natural riboseries 27, and started from the bicyclic sugar analog 1 and the nitrobase 2.
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. Pdf importance of the reverse hoogsteen base pair 5458. The structures and relative stabilities of dgg dna crystals. In contrast to wastoncrick wc base pairing, the purine base component is flipped from anti to synconformation. Synthesis and base pairing of oligonucleotides containing 1. Sep 14, 2005 we have solved the crystal structure of human dna polymerase. Jan 26, 2011 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 base pairing. Dna duplexes predominantly contain watsoncrick wc base pairs. Pdf a hoogsteen base pair embedded in undistorted bdna. Peptide nucleic acids pnas are nucleic acid analogs with the deoxyribose phosphate backbone replaced by pseudopeptide polymers to which the nucleobases are linked. We show that bpi derivatives bind to hoogsteen basepaired duplexes and stabilize them. Characterizing watsoncrick versus hoogsteen base pairing. Dec 27, 2019 hoogsteen and watsoncrick base pairings.
However, the contribution of each hoogsteen base pair at different positions to whole stability of the gquadruplex has not been known. View enhanced pdf access article on wiley online library html view download pdf for offline viewing. Pdf transient hoogsteen base pairs in canonical duplex dna. Mar 05, 2002 although watsoncrick base pairing is always preserved, the nmr data 911 cannot exclude the presence of a minor hoogsteen component. A characteristic feature of hoogsteen base pairing is that the n7 position of the purine is base paired, altering the chemical reactivity of this position. The observation of hoogsteen basepairs 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 basepairs as a means of expanding its structural complexity beyond that which can be achieved based on watsoncrick basepairing. The hoogsteen base pairs fit the electron density map throughout the structure. Stabilization of hoogsteen base pairing by introduction of. Hydrogen bond patterns for an adeninethymine at base pair. Energy landscape and pathways for transitions between. Ghosal, gargi and muniyappa, k 2006 hoogsteen basepairing revisited. In contrast to previously reported p53dna complexes that show standard watsoncrick base pairs, the newly reported structures show noncanonical hoogsteen base pairing geometry at the central at doublet of each halfsite. Basically, hoogsteen pairing is normal watsoncrick base pairing only flipped over, allowing for new geometry and new conformations such as the gquadruplex described above.
The structures and relative stabilities of dgg reverse hoogsteen, dgt reverse wobble, and dgc reverse watsoncrick basepairs in dna crystals blaineh. Introduction pictures of the double helix of deoxyribonucleic acid. Atomistic insight into the kinetic pathways for watson. T of the dimer with the incoming a has been proposed for pol here we examine the mechanisms of cpd bypass by dpo4 and pol. In this manner, two nucleobases, one on each strand, can be held together by hydrogen bonds in the major groove. C and d show time traces for the hydrogen bond distances of a 200 ns md simulation in c wc and d hg, with probability histograms showing the accumulated data for c 9 and d 5 individual. The au or at hoogsteen pair is a wellknown type of base pair bp, named after the scientist who discovered it. Research paper hoogsteen pairing in bicycledna bolli et al. The formation of a tri base pairing from free nucleobases is rare. Stabilization of hoogsteen base pairing by introduction of nh 2 group at the c8 position of adenine.
For example, the first triple helix discovered, polyupolyapolyu, has an allpurine strand pur paired with two allpyrimidine strands pyr. The rules of base pairing tell us that if we can read the sequence of nucleotides on one strand of dna, we can immediately deduce the complementary sequence on the other strand. 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. In the case of polydat 12, it has been suggested that c form dna is formed at premelting temperatures, but from the evidence presented it cannot be excluded that hoogsteen dna might be responsible. We have solved the crystal structure of human dna polymerase. European synchrotron radiation facility, bp 220, f38043 grenoble, france. Crystal structure of an antiparallel dna fragment with. However, the contribution of each hoogsteen basepair at different positions to whole stability of the gquadruplex has not been known. There are three main types of noncanonical base pairs. The recent discovery that hoogsteen hg base pairs are widespread in dna across diverse sequences and positional contexts could have important implications for understanding dna replication and dnaprotein recognition. Pdf hoogsteen hg base pairs bps provide an alternative pairing geometry to watsoncrick wc bps and can. Another form of base pairing is known as hoogsteen base pairs, but in this conformation the g. 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. Effects of deficient of the hoogsteen basepairs on the gquadruplex.
1308 907 1327 844 1443 205 280 567 1436 1470 424 1151 537 1441 1320 582 1305 202 1351 516 127 1452 887 784 359 174 154 1185 750 672 989 99 620 778 1277 1110 714 1447 633 1082 1259 1029 471