The structure of the holliday junction, and its resolution

Duckett, Derek R.; Murchie, Alastair I. H.; Diekmann, Stephan; Kitzing, Eberhard Von; Kemper, Börries; Lilley, David M.J.

doi:10.1016/0092-8674(88)90011-6

Cited by 482 publications

(677 citation statements)

References 28 publications

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“…These two four-arm junctions have exactly the same sequence of base pairs at the branching point but differ in terms of the base pairs in the penultimate position. Experiments on synthetic HJ systems using low-resolution techniques have been universal in supporting the belief that the penultimate base pairs have no influence on the crossover isomer preference (11,13,14,16). Hence, the approximately 4-fold difference in the isomer preferences of J2 and J2P1 was not anticipated.…”

Section: Discussionmentioning

confidence: 80%

“…For 15 N-labeled J1 and J2, all seven oligonucleotides were synthesized by Keystone Laboratories (Menlo Park, CA). For the one strand common to both J1 and J2, [1,[3][4][5][6][7][8][9][10][11][12][13][14][15] N]thymidine phosphoramidite (synthesized by the National Stable Isotope Resource, Los Alamos, NM) was used for the thymidine at position 9. Purification by anion-exchange chromatography was carried out using HQ POROS resin in an 8-ml column on a Biocad Sprint (PerCeptives Biosystems, Cambridge, MA).…”

Section: Methodsmentioning

confidence: 99%

“…2). The junction at which the four duplex arms meet and the strands cross over is termed the branching point.In vitro studies of the structure of partially and completely immobilized Holliday junctions by gel mobility and chemical and enzymatic footprinting revealed dominant crossover isomer preferences (11)(12)(13)(14)(15)(16)(17). Minor cleavage sites were occasionally observed in restriction enzyme cleavage experiments, and the possibility of this arising from the presence of a small amount of the alternative crossover isomer was discussed (e.g., refs.…”

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confidence: 99%

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Crossover isomer bias is the primary sequence-dependent property of immobilized Holliday junctions

Miick

Fee

Millar

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

109

101

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Recombination of genes is essential to the evolution of genetic diversity, the segregation of chromosomes during cell division, and certain DNA repair processes. The Holliday junction, a four-arm, four-strand branched DNA crossover structure, is formed as a transient intermediate during genetic recombination and repair processes in the cell. The recognition and subsequent resolution of Holliday junctions into parental or recombined products appear to be critically dependent on their three-dimensional structure. Complementary NMR and time-resolved f luorescence resonance energy transfer experiments on immobilized four-arm DNA junctions reported here indicate that the Holliday junction cannot be viewed as a static structure but rather as an equilibrium mixture of two conformational isomers. Furthermore, the distribution between the two possible crossover isomers was found to depend on the sequence in a manner that was not anticipated on the basis of previous low-resolution experiments.Genetic recombination is a primary biological process that is critical to the continual evolution of all organisms, and the Holliday junction is a requisite intermediate in nearly all recombination events. Holliday (1) proposed the first and most basic mechanism of genetic recombination: homologous chromatids are nicked at identical sites, then the duplex DNA is partially unwound and the single strands are paired with the complementary strands of the homologs. The structure thus formed, termed the Holliday junction (HJ), may travel (branch-migrate) in either direction along the DNA. Eventually, the structure is cut endonucleolytically (resolved) to give two chromosomes with either a parental (patch) or a recombined (splice) configuration (Fig. 1). Although many postulated mechanisms for recombination exist, they differ only in how recombination is initiated and in how DNA strands are displaced (1-5). Most recombination mechanisms invoke formation of heteroduplex DNA molecules containing branched structures.It has been reported for more than 40 years that DNA sequence at or near a HJ influences how it is resolved and the corresponding ratio of parental to recombined molecules (6).Results from a variety of experiments suggest that resolution must be predetermined for certain sequences and that not all HJs are identical in structure (e.g., refs. 7-10). To gain an in-depth understanding of recognition and resolution of HJs, it is imperative to characterize their structure and dynamics at the atomic level and to establish how these properties vary with sequence.A consensus view of HJ structure has emerged from biophysical studies of immobilized four-arm DNA junctions in which the sequence is designed to eliminate the possibility of branch migration (for reviews see refs. 11 and 12). The four helical arms are seen to stack upon each other in a pairwise fashion, forming two duplex domains with an acute interhelical angle (Fig. 2). In this configuration, two contiguous strands run antiparallel to each other and the two crossover stra...

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Section: Discussionmentioning

confidence: 80%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Crossover isomer bias is the primary sequence-dependent property of immobilized Holliday junctions

Miick

Fee

Millar

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

109

101

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“…With model substrates it was shown that the structure of the junction is sensitive to the presence of divalent metal ions which facilitate their folding into a "stacked X-structure," in which the arms of the junction are antiparallel (7)(8)(9)(10). The stacked X-structure exhibits twofold symmetry with two strands approximating B-form DNA (defined as the continuous strands), while the complementary strands are sharply bent where they pass from one helix to the other (7,8). It is these crossover (or exchanging) strands that are cut by T4 endonuclease VII, a bacteriophage-encoded resolvase (11,12).…”

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confidence: 99%

RuvC protein resolves Holliday junctions via cleavage of the continuous (noncrossover) strands.

Bennett¹,

West²

1995

Proc. Natl. Acad. Sci. U.S.A.

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The RuvC protein ofEscherichia coli resolves Holliday junctions during genetic recombination and the postreplicational repair of DNA damage. Using synthetic Holliday junctions that are constrained to adopt defined isomeric configurations, we show that resolution occurs by symmetric cleavage of the continuous (noncrossing) pair of DNA strands. This result contrasts with that observed with phage T4 endonuclease VII, which cleaves the pair of crossing strands. In the presence of RuvC, the pair of continuous strands (i.e., the target strands for cleavage) exhibit a hypersensitivity to hydroxyl radicals. These results indicate that the continuous strands are distorted within the RuvC/Holliday junction complex and that RuvC-mediated resolution events require protein-directed structural changes to the four-way junction.

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“…In general, branched junctions formed from single helices are floppy and tend to cyclize into families of trimers, tetramers, and higher macrocycles. In particular, fourarmed branch junctions vacillate between one of two different "stacked-X" conformations [20,21] and, demonstrating a mind of their own, assume a 60 degree angle rather than the 90 degree angle one might like them too. Again by trashing symmetries, one can use specific sticky ends that force a particular connectivity, such as the DNA cube [1], but because of uncertainty in the junction geometry, it is still unknown whether the DNA cube was cube or some other parallelopiped.…”

Section: Dna Origami For Polygonal Networkmentioning

confidence: 99%

Scaffolded DNA Origami: from Generalized Multicrossovers to Polygonal Networks

Rothemund

Natural Computing Series

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My acquaintance with Ned Seeman began in the Caltech library sometime during 1992. At the time I was trying to design a DNA computer and was collecting papers in an attempt to learn all the biochemical tricks ever performed with DNA. Among the papers was Ned and Junghuei Chen's beautiful construction of a DNA cube [1]. I had no idea how to harness such a marvel for computation -the diagrams explaining the cube were in a visual language that I could not parse and its static structure, once formed, did not seem to allow further information processing. However, I was in awe of the cube and wondered what kind of mad and twisted genius had conjured it.Ned's DNA sculptures did turn out to have a relationship to computation. In 1994 Len Adleman's creation of a DNA computer [2] showed that linear DNA self-assembly, together with operations such as PCR, could tackle NP-complete computational problems. Excited by this result, Erik Winfree quickly forged an amazing link that showed how the self-assembly of geometrical DNA objects, alone, can perform universal computation [3]. The demonstration and exploration of this link has kept a small gaggle of computer scientists and mathematicians tangled up with Ned and his academic children for the last decade. At an intellectual level the technical achievements of the resulting collaborations and interactions have been significant, among them the first two-dimensional DNA crystals [4] and algorithmic self-assembly of both linear [5] and two-dimensional [6] arrays. By various other paths, a number of physicists have joined the party, mixing their own ideas with Ned's paradigm of "DNA as tinkertoys" to create nanomechanical systems such as DNA tweezers [7] and walkers [8,9,10]. DNA nanotechnology has taken on a life of its own since Ned's original vision of DNA fish flying in an extended Escherian lattice [11] and we look forward to a new "DNA world" in which an all-DNA "bacterium" wriggles, reproduces and computes.On a personal level, I and many others have gotten to find out exactly what kind of twisted genius Ned is. Ned is a singular character. He is at once gruff and caring, vulgar and articulate, stubborn and visionary. Ned is generous both with his knowledge of DNA and his knowledge of life. His

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The structure of the holliday junction, and its resolution

Cited by 482 publications

References 28 publications

Crossover isomer bias is the primary sequence-dependent property of immobilized Holliday junctions

Crossover isomer bias is the primary sequence-dependent property of immobilized Holliday junctions

RuvC protein resolves Holliday junctions via cleavage of the continuous (noncrossover) strands.

Scaffolded DNA Origami: from Generalized Multicrossovers to Polygonal Networks

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