cruciform dna


Summary: A cross-shaped DNA structure that can be observed under the electron microscope. It is formed by the incomplete exchange of strands between two double-stranded helices or by complementary INVERTED REPEAT SEQUENCES that refold into hairpin loops on opposite strands across from each other.

Top Publications

  1. Donaldson J, Courcelle C, Courcelle J. RuvABC is required to resolve holliday junctions that accumulate following replication on damaged templates in Escherichia coli. J Biol Chem. 2006;281:28811-21 pubmed
    ..A model is proposed in which RuvABC is required to resolve junctions that arise during the repair of a subset of nonarresting lesions after replication has passed through the template. ..
  2. Kepple K, Boldt J, Segall A. Holliday junction-binding peptides inhibit distinct junction-processing enzymes. Proc Natl Acad Sci U S A. 2005;102:6867-72 pubmed
    ..These inhibitors should be extremely useful for dissecting homologous recombination and recombination-dependent repair in vitro and in vivo. ..
  3. Liu J, Déclais A, Lilley D. Electrostatic interactions and the folding of the four-way DNA junction: analysis by selective methyl phosphonate substitution. J Mol Biol. 2004;343:851-64 pubmed
  4. Déclais A, Lilley D. New insight into the recognition of branched DNA structure by junction-resolving enzymes. Curr Opin Struct Biol. 2008;18:86-95 pubmed
    ..The comparison highlights the versatility of Holliday junction resolution, and extracts some general principles of recognition. ..
  5. Gari K, Décaillet C, Stasiak A, Stasiak A, Constantinou A. The Fanconi anemia protein FANCM can promote branch migration of Holliday junctions and replication forks. Mol Cell. 2008;29:141-8 pubmed publisher
    ..6 kb of DNA. Our data suggest a direct role for FANCM in DNA processing, consistent with the current view that FA proteins coordinate DNA repair at stalled replication forks. ..
  6. Fouché N, Cesare A, Willcox S, Ozgur S, Compton S, Griffith J. The basic domain of TRF2 directs binding to DNA junctions irrespective of the presence of TTAGGG repeats. J Biol Chem. 2006;281:37486-95 pubmed
    ..Junction-specific binding would also allow TRF2 to stabilize a strand invasion structure that is thought to exist at the strand invasion site of the t-loop. ..
  7. Yamada K, Ariyoshi M, Morikawa K. Three-dimensional structural views of branch migration and resolution in DNA homologous recombination. Curr Opin Struct Biol. 2004;14:130-7 pubmed
    ..The mechanism of junction resolution by RuvC in the RuvABC resolvasome remains to be elucidated. ..
  8. Whitby M. Making crossovers during meiosis. Biochem Soc Trans. 2005;33:1451-5 pubmed
    ..The second pathway appears to involve the cleavage of the precursors of ligated HJs, namely displacement (D) loops and unligated/nicked HJs, by the Mus81-Eme1/Mms4 endonuclease. ..
  9. Bishop D, Zickler D. Early decision; meiotic crossover interference prior to stable strand exchange and synapsis. Cell. 2004;117:9-15 pubmed
    ..Chromosome synapsis occurs after CO/NCO designation and is not required for the regulated distribution of COs along chromosomes manifested as CO interference. ..

More Information


  1. Compton S, Tolun G, Kamath Loeb A, Loeb L, Griffith J. The Werner syndrome protein binds replication fork and holliday junction DNAs as an oligomer. J Biol Chem. 2008;283:24478-83 pubmed publisher
    ..Calculations of the molecular weight of full-length WRN revealed that, in solution, WRN exists predominantly as a dimer. However, WRN bound to DNA is larger; the mass is consistent with that of a tetramer. ..
  2. Khuu P, Voth A, Hays F, Ho P. The stacked-X DNA Holliday junction and protein recognition. J Mol Recognit. 2006;19:234-242 pubmed publisher
    ..This review focuses on the sequence dependent structure of the stacked-X junction and how it may play a role in structural recognition by a class of dimeric junction resolving enzymes that themselves show no direct sequence recognition. ..
  3. Wu B, Girard F, van Buuren B, SCHLEUCHER J, Tessari M, Wijmenga S. Global structure of a DNA three-way junction by solution NMR: towards prediction of 3H fold. Nucleic Acids Res. 2004;32:3228-39 pubmed
    ..Together, these findings open up the possibility of full prediction of 3HS2 conformation (stacking and global fold) directly from sequence. ..
  4. Raynard S, Bussen W, Sung P. A double Holliday junction dissolvasome comprising BLM, topoisomerase IIIalpha, and BLAP75. J Biol Chem. 2006;281:13861-4 pubmed
    ..This function of the BLM-Topo IIIalpha-BLAP75 dissolvasome is likely indispensable for genome maintenance and cancer avoidance. ..
  5. Cromie G, Hyppa R, Taylor A, Zakharyevich K, Hunter N, Smith G. Single Holliday junctions are intermediates of meiotic recombination. Cell. 2006;127:1167-78 pubmed
  6. Biswas T, Aihara H, Radman Livaja M, Filman D, Landy A, Ellenberger T. A structural basis for allosteric control of DNA recombination by lambda integrase. Nature. 2005;435:1059-66 pubmed
    ..An intertwined layer of amino-terminal domains bound to accessory (arm) DNAs shapes the recombination complex in a way that suggests how arm binding shifts the reaction equilibrium in favour of recombinant products. ..
  7. Gaskell L, Osman F, Gilbert R, Whitby M. Mus81 cleavage of Holliday junctions: a failsafe for processing meiotic recombination intermediates?. EMBO J. 2007;26:1891-901 pubmed
    ..We also present genetic evidence that suggests that this activity might be utilised as a back-up to Mus81-Eme1's main activity of cleaving nicked HJs during meiosis in S. pombe. ..
  8. Geuting V, Kobbe D, Hartung F, Dürr J, Focke M, Puchta H. Two distinct MUS81-EME1 complexes from Arabidopsis process Holliday junctions. Plant Physiol. 2009;150:1062-71 pubmed publisher
    ..Our results are in line with an involvement of both MUS81-EME1 endonuclease complexes in DNA recombination and repair processes in Arabidopsis. ..
  9. Mikheikin A, Lushnikov A, Lyubchenko Y. Effect of DNA supercoiling on the geometry of holliday junctions. Biochemistry. 2006;45:12998-3006 pubmed
    ..Altogether, the data obtained show directly that DNA supercoiling is the major factor determining the Holliday junction conformation. ..
  10. Bugreev D, Mazina O, Mazin A. Rad54 protein promotes branch migration of Holliday junctions. Nature. 2006;442:590-3 pubmed
    ..13). Novel DNA branch-migration activity is fully consistent with this late homologous recombination function of Rad54 protein. ..
  11. Machwe A, Xiao L, Lloyd R, Bolt E, Orren D. Replication fork regression in vitro by the Werner syndrome protein (WRN): holliday junction formation, the effect of leading arm structure and a potential role for WRN exonuclease activity. Nucleic Acids Res. 2007;35:5729-47 pubmed
    ..These findings, along with the established cellular consequences of WRN deficiency, strongly support a role for WRN in regression of blocked replication forks. ..
  12. Losch F, Bredenbeck A, Hollstein V, Walden P, Wrede P. Evidence for a large double-cruciform DNA structure on the X chromosome of human and chimpanzee. Hum Genet. 2007;122:337-43 pubmed
    ..of a high number of large inverted repeat (IR) DNA sequences which fulfill all requirements for formation of cruciform DNA structures...
  13. Waldmann T, Baack M, Richter N, Gruss C. Structure-specific binding of the proto-oncogene protein DEK to DNA. Nucleic Acids Res. 2003;31:7003-10 pubmed
    ..DEK also increases the probability of intermolecular ligation of linear DNA molecules by DNA ligase. These binding properties qualify DEK as an architectural protein. ..
  14. Tarsounas M, Muñoz P, Claas A, Smiraldo P, Pittman D, Blasco M, et al. Telomere maintenance requires the RAD51D recombination/repair protein. Cell. 2004;117:337-47 pubmed
    ..We conclude that RAD51D plays a dual cellular role in both the repair of DNA double-strand breaks and telomere protection against attrition and fusion. ..
  15. McMahill M, Sham C, Bishop D. Synthesis-dependent strand annealing in meiosis. PLoS Biol. 2007;5:e299 pubmed
    ..This diagnostic class represents 26% of selected NCO recombinants. Tetrad analysis using the same markers provided additional evidence that SDSA is a major pathway for NCO gene conversion in meiosis. ..
  16. Ghosh K, Lau C, Guo F, Segall A, Van Duyne G. Peptide trapping of the Holliday junction intermediate in Cre-loxP site-specific recombination. J Biol Chem. 2005;280:8290-9 pubmed
    ..Peptide binding induces large conformational changes in the DNA strands of the HJ intermediate, which affect the active site geometries in the recombinase subunits. ..
  17. Dawid A, Croquette V, Grigoriev M, Heslot F. Single-molecule study of RuvAB-mediated Holliday-junction migration. Proc Natl Acad Sci U S A. 2004;101:11611-6 pubmed
    ..The average migration rate at zero load was found to be approximately 43 bp/sec. Furthermore, the load dependence of the migration rate is small, within the force range of -3.4 pN (hindering force) to +3.4 pN (assisting force). ..
  18. Liu Y, Masson J, Shah R, O Regan P, West S. RAD51C is required for Holliday junction processing in mammalian cells. Science. 2004;303:243-6 pubmed
    ..We conclude that the RAD51 paralogs are involved in HJ processing in human cells. ..
  19. Ralf C, Hickson I, Wu L. The Bloom's syndrome helicase can promote the regression of a model replication fork. J Biol Chem. 2006;281:22839-46 pubmed
    ..These data establish the existence of a eukaryotic protein that could promote replication fork regression in vivo and suggest a novel pathway through which BLM might suppress genetic exchanges. ..
  20. Poulet A, Buisson R, Faivre Moskalenko C, Koelblen M, Amiard S, Montel F, et al. TRF2 promotes, remodels and protects telomeric Holliday junctions. EMBO J. 2009;28:641-51 pubmed publisher
  21. Haber J, Ira G, Malkova A, Sugawara N. Repairing a double-strand chromosome break by homologous recombination: revisiting Robin Holliday's model. Philos Trans R Soc Lond B Biol Sci. 2004;359:79-86 pubmed
  22. Hazelbaker D, Azaro M, Landy A. A biotin interference assay highlights two different asymmetric interaction profiles for lambda integrase arm-type binding sites in integrative versus excisive recombination. J Biol Chem. 2008;283:12402-14 pubmed publisher
  23. Carrasco B, Cozar M, Lurz R, Alonso J, Ayora S. Genetic recombination in Bacillus subtilis 168: contribution of Holliday junction processing functions in chromosome segregation. J Bacteriol. 2004;186:5557-66 pubmed
  24. Radman Livaja M, Biswas T, Mierke D, Landy A. Architecture of recombination intermediates visualized by in-gel FRET of lambda integrase-Holliday junction-arm DNA complexes. Proc Natl Acad Sci U S A. 2005;102:3913-20 pubmed
  25. Fujikane R, Komori K, Shinagawa H, Ishino Y. Identification of a novel helicase activity unwinding branched DNAs from the hyperthermophilic archaeon, Pyrococcus furiosus. J Biol Chem. 2005;280:12351-8 pubmed
    ..The Hjm helicase may play a central role in the repair systems of organisms living in extreme environments. ..
  26. Kuznetsov S, Pellegrini M, Shuda K, Fernandez Capetillo O, Liu Y, Martin B, et al. RAD51C deficiency in mice results in early prophase I arrest in males and sister chromatid separation at metaphase II in females. J Cell Biol. 2007;176:581-92 pubmed
    ..Based on the marked reduction in Holliday junction (HJ) resolution activity in Rad51c-null mouse embryonic fibroblasts, we propose that this late function may be associated with HJ resolution. ..
  27. Kobbe D, Blanck S, Demand K, Focke M, Puchta H. AtRECQ2, a RecQ helicase homologue from Arabidopsis thaliana, is able to disrupt various recombinogenic DNA structures in vitro. Plant J. 2008;55:397-405 pubmed publisher
    ..The biochemical properties defined in this work support the hypothesis that AtRECQ2 might be functionally orthologous to the helicase part of the human RecQ homologue HsWRN. ..
  28. Tripathi P, Anuradha S, Ghosal G, Muniyappa K. Selective binding of meiosis-specific yeast Hop1 protein to the holliday junctions distorts the DNA structure and its implications for junction migration and resolution. J Mol Biol. 2006;364:599-611 pubmed
    ..We propose that Hop1 protein might coordinate the physical monitoring of meiotic recombination intermediates with the process of branch migration of Holliday junction. ..
  29. Hadden J, D clais A, Carr S, Lilley D, Phillips S. The structural basis of Holliday junction resolution by T7 endonuclease I. Nature. 2007;449:621-4 pubmed publisher
    ..These interactions effectively measure the relative orientations and positions of the arms of the junction, thereby ensuring that binding is selective for branched DNA that can achieve this geometry...
  30. Sanchez H, Kidane D, Reed P, Curtis F, Cozar M, Graumann P, et al. The RuvAB branch migration translocase and RecU Holliday junction resolvase are required for double-stranded DNA break repair in Bacillus subtilis. Genetics. 2005;171:873-83 pubmed
    ..The results demonstrate that, as with E. coli RuvABC, RuvAB targets RecU to recombination intermediates and that all three proteins are required for repair of DSBs arising from lesions in chromosomal DNA. ..
  31. Oh S, Lao J, Hwang P, Taylor A, Smith G, Hunter N. BLM ortholog, Sgs1, prevents aberrant crossing-over by suppressing formation of multichromatid joint molecules. Cell. 2007;130:259-72 pubmed
    ..Thus, by disrupting aberrant JMs, BLM-related helicases maximize repair efficiency while minimizing the risk of deleterious crossing-over. ..
  32. Inagaki H, Ohye T, Kogo H, Yamada K, Kowa H, Shaikh T, et al. Palindromic AT-rich repeat in the NF1 gene is hypervariable in humans and evolutionarily conserved in primates. Hum Mutat. 2005;26:332-42 pubmed
    ..Although such palindromic regions are usually unstable and disappear rapidly due to deletion, the 17PATRR in the NF1 gene was stably conserved during evolution for reasons that are still unknown. ..
  33. Guy C, Bolt E. Archaeal Hel308 helicase targets replication forks in vivo and in vitro and unwinds lagging strands. Nucleic Acids Res. 2005;33:3678-90 pubmed publisher
    ..We speculate that removal of lagging strands at stalled forks by Hel308 promotes the formation of initiation zones, priming restart of lagging strand synthesis...
  34. Wu L, Chan K, Ralf C, Bernstein D, Garcia P, Bohr V, et al. The HRDC domain of BLM is required for the dissolution of double Holliday junctions. EMBO J. 2005;24:2679-87 pubmed
    ..Furthermore, we show that lysine-1270 of BLM, which resides in the HRDC domain and is predicted to play a role in mediating interactions with DNA, is required for efficient dissolution. ..
  35. Wu L, Hickson I. The Bloom's syndrome helicase suppresses crossing over during homologous recombination. Nature. 2003;426:870-4 pubmed
    ..These results have wider implications for our understanding of the process of homologous recombination and the mechanisms that exist to prevent tumorigenesis. ..
  36. Hollingsworth N, Brill S. The Mus81 solution to resolution: generating meiotic crossovers without Holliday junctions. Genes Dev. 2004;18:117-25 pubmed
  37. Garcia P, Liu Y, Jiricny J, West S, Janscak P. Human RECQ5beta, a protein with DNA helicase and strand-annealing activities in a single polypeptide. EMBO J. 2004;23:2882-91 pubmed
    ..This is the first demonstration of a DNA helicase with an intrinsic DNA strand-annealing function residing in a separate domain. ..
  38. Stefanovsky V, Moss T. The cruciform DNA mobility shift assay: a tool to study proteins that recognize bent DNA. Methods Mol Biol. 2009;543:537-46 pubmed publisher
    ..In contrast, such proteins often bind prebent DNAs with high affinity and specificity. A synthetic cruciform DNA structure will often provide an ideal binding site for such proteins, allowing their affinities for both bent ..
  39. Gunderson C, Segall A. DNA repair, a novel antibacterial target: Holliday junction-trapping peptides induce DNA damage and chromosome segregation defects. Mol Microbiol. 2006;59:1129-48 pubmed
    ..Inhibition of DNA repair constitutes a novel target of antibiotic therapy. The peptides affect targets that arise in multiple pathways, and as expected, are quite resistant to the development of spontaneous antibiotic resistance. ..
  40. Börner G, Kleckner N, Hunter N. Crossover/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell. 2004;117:29-45 pubmed
  41. Mazina O, Mazin A, Nakagawa T, Kolodner R, Kowalczykowski S. Saccharomyces cerevisiae Mer3 helicase stimulates 3'-5' heteroduplex extension by Rad51; implications for crossover control in meiotic recombination. Cell. 2004;117:47-56 pubmed
  42. Chang J, Kim J, Choi J, Lee J, Cho Y. Crystal structure of the Mus81-Eme1 complex. Genes Dev. 2008;22:1093-106 pubmed publisher
  43. Dennis C, Fedorov A, Käs E, Salomé L, Grigoriev M. RuvAB-directed branch migration of individual Holliday junctions is impeded by sequence heterology. EMBO J. 2004;23:2413-22 pubmed
    ..We conclude that translocation of the junctions through a sequence heterology occurs with a probability of bypass being determined both by the length of the heterologous region and the lifetime of the stalled RuvAB complex. ..
  44. Kurahashi H, Inagaki H, Yamada K, Ohye T, Taniguchi M, Emanuel B, et al. Cruciform DNA structure underlies the etiology for palindrome-mediated human chromosomal translocations. J Biol Chem. 2004;279:35377-83 pubmed
    ..Furthermore, anti-cruciform DNA antibody reduces the electrophoretic mobility of the PATRR-containing fragment...
  45. Amit R, Gileadi O, Stavans J. Direct observation of RuvAB-catalyzed branch migration of single Holliday junctions. Proc Natl Acad Sci U S A. 2004;101:11605-10 pubmed
    ..The apparent processivity of branch migration between pauses of inactivity is approximately 7,000 bp. Branch migration persists against opposing forces up to 23 pN. ..
  46. Middleton C, Parker J, Richard D, White M, Bond C. Substrate recognition and catalysis by the Holliday junction resolving enzyme Hje. Nucleic Acids Res. 2004;32:5442-51 pubmed publisher
    ..The loop may act as a conformational switch, ensuring that the active site is completed only on binding a four-way junction, thus explaining the exquisite specificity of these enzymes...
  47. Rajeev L, Segall A, Gardner J. The bacteroides NBU1 integrase performs a homology-independent strand exchange to form a holliday junction intermediate. J Biol Chem. 2007;282:31228-37 pubmed
    ..The possible mechanisms by which the mismatches stimulate recombination are discussed. ..
  48. Bussen W, Raynard S, Busygina V, Singh A, Sung P. Holliday junction processing activity of the BLM-Topo IIIalpha-BLAP75 complex. J Biol Chem. 2007;282:31484-92 pubmed
  49. Privezentzev C, Keeley A, Sigala B, Tsaneva I. The role of RuvA octamerization for RuvAB function in vitro and in vivo. J Biol Chem. 2005;280:3365-75 pubmed
    ..Significantly, the mutant failed to complement the UV sensitivity of E. coli DeltaruvA cells. These results indicate strongly that RuvA octamerization is essential for the full biological activity of RuvABC. ..
  50. Briggs G, Mahdi A, Wen Q, Lloyd R. DNA binding by the substrate specificity (wedge) domain of RecG helicase suggests a role in processivity. J Biol Chem. 2005;280:13921-7 pubmed
    ..This keeps the helicase motor in contact with the substrate, enabling it to drive dsDNA translocation with high efficiency. ..
  51. McKinney S, Freeman A, Lilley D, Ha T. Observing spontaneous branch migration of Holliday junctions one step at a time. Proc Natl Acad Sci U S A. 2005;102:5715-20 pubmed
  52. Karymov M, Daniel D, Sankey O, Lyubchenko Y. Holliday junction dynamics and branch migration: single-molecule analysis. Proc Natl Acad Sci U S A. 2005;102:8186-91 pubmed
    ..The conformational flip and the variable base pair hopping step provide insights into the regulatory mechanism of genetic processes involving HJs. ..
  53. Ira G, Malkova A, Liberi G, Foiani M, Haber J. Srs2 and Sgs1-Top3 suppress crossovers during double-strand break repair in yeast. Cell. 2003;115:401-11 pubmed
    ..Srs2 promotes the noncrossover synthesis-dependent strand-annealing (SDSA) pathway, apparently by regulating Rad51 binding during strand exchange. ..