nucleic acid heteroduplexes


Summary: Double-stranded nucleic acid molecules (DNA-DNA or DNA-RNA) which contain regions of nucleotide mismatches (non-complementary). In vivo, these heteroduplexes can result from mutation or genetic recombination; in vitro, they are formed by nucleic acid hybridization. Electron microscopic analysis of the resulting heteroduplexes facilitates the mapping of regions of base sequence homology of nucleic acids.

Top Publications

  1. Mitchel K, Zhang H, Welz Voegele C, Jinks Robertson S. Molecular structures of crossover and noncrossover intermediates during gap repair in yeast: implications for recombination. Mol Cell. 2010;38:211-22 pubmed publisher
  2. Myong S, Cui S, Cornish P, Kirchhofer A, Gack M, Jung J, et al. Cytosolic viral sensor RIG-I is a 5'-triphosphate-dependent translocase on double-stranded RNA. Science. 2009;323:1070-4 pubmed publisher
    ..This functional integration of two RNA molecular patterns may provide a means to specifically sense and counteract replicating viruses. ..
  3. Ohtani N, Tomita M, Itaya M. Junction ribonuclease activity specified in RNases HII/2. FEBS J. 2008;275:5444-55 pubmed publisher
    ..In addition, although the activity has been reported not to occur on completely single-stranded RNA-DNA, it can recognize a single-stranded RNA-DNA junction if a double-stranded region is located adjacent to the junction. ..
  4. Juliano J, Trottman P, Mwapasa V, Meshnick S. Detection of the dihydrofolate reductase-164L mutation in Plasmodium falciparum infections from Malawi by heteroduplex tracking assay. Am J Trop Med Hyg. 2008;78:892-4 pubmed
    ..Using this assay, we confirmed the presence of the mutation in P. falciparum infections in Malawi. ..
  5. Juliano J, Kwiek J, Cappell K, Mwapasa V, Meshnick S. Minority-variant pfcrt K76T mutations and chloroquine resistance, Malawi. Emerg Infect Dis. 2007;13:872-7 pubmed
    ..Surveillance for minority-variant drug resistant mutations may be useful in making antimalarial drug policy. ..
  6. Radford S, Sabourin M, McMahan S, Sekelsky J. Meiotic recombination in Drosophila Msh6 mutants yields discontinuous gene conversion tracts. Genetics. 2007;176:53-62 pubmed
    ..We suggest that these discontinuities reflect the activity of a short-patch repair system that operates when canonical MMR is defective. ..
  7. Radford S, McMahan S, Blanton H, Sekelsky J. Heteroduplex DNA in meiotic recombination in Drosophila mei-9 mutants. Genetics. 2007;176:63-72 pubmed
  8. York S, Modrich P. Mismatch repair-dependent iterative excision at irreparable O6-methylguanine lesions in human nuclear extracts. J Biol Chem. 2006;281:22674-83 pubmed
    ..These results provide the first direct evidence for mismatch repair-mediated iterative processing of DNA methylator damage, an effect that may be relevant to damage signaling events triggered by this class of chemotherapeutic agent. ..
  9. Bode J, Winkelmann S, Götze S, Spiker S, Tsutsui K, Bi C, et al. Correlations between scaffold/matrix attachment region (S/MAR) binding activity and DNA duplex destabilization energy. J Mol Biol. 2006;358:597-613 pubmed

More Information


  1. Nowotny M, Gaidamakov S, Crouch R, Yang W. Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysis. Cell. 2005;121:1005-16 pubmed
    ..In transposases, they are symmetrically coordinated and exchange roles to alternately activate a water and a 3'-OH for successive strand cleavage and transfer by a ping-pong mechanism. ..
  2. Ngrenngarmlert W, Kwiek J, Kamwendo D, Ritola K, Swanstrom R, Wongsrichanalai C, et al. Measuring allelic heterogeneity in Plasmodium falciparum by a heteroduplex tracking assay. Am J Trop Med Hyg. 2005;72:694-701 pubmed
    ..This study is a proof of concept that HTA is a sensitive allelic discrimination method able to determine genetic diversity in P. falciparum and warrants its use in studies of antimalarial drug efficacy. ..
  3. Huang Y, Chen S, Goodman S, Wu S, Kao J, Lee C, et al. Interaction of nick-directed DNA mismatch repair and loop repair in human cells. J Biol Chem. 2004;279:30228-35 pubmed
    ..We propose a model in which DNA repair systems avoid simultaneous repair at adjacent sites to avoid the creation of double-stranded DNA breaks. ..
  4. Jensen L, Jauert P, Kirkpatrick D. The large loop repair and mismatch repair pathways of Saccharomyces cerevisiae act on distinct substrates during meiosis. Genetics. 2005;170:1033-43 pubmed
    ..Our data reveal differences in mitotic and meiotic MMR and LLR; these may be due to alterations in the functioning of each complex or result from subtle sequence context influences on repair of the various mismatches examined. ..
  5. Corrette Bennett S, Borgeson C, Sommer D, Burgers P, Lahue R. DNA polymerase delta, RFC and PCNA are required for repair synthesis of large looped heteroduplexes in Saccharomyces cerevisiae. Nucleic Acids Res. 2004;32:6268-75 pubmed
    ..These biochemical experiments support the idea that yeast polymerase delta, RFC and PCNA are required for large loop DNA repair synthesis. ..
  6. Langston L, Symington L. Gene targeting in yeast is initiated by two independent strand invasions. Proc Natl Acad Sci U S A. 2004;101:15392-7 pubmed
  7. Allers T, Lichten M. Intermediates of yeast meiotic recombination contain heteroduplex DNA. Mol Cell. 2001;8:225-31 pubmed
    ..Such structures are not easily accommodated by the canonical version of the double-strand break repair model. ..
  8. Raynard S, Baker M. Incorporation of large heterologies into heteroduplex DNA during double-strand-break repair in mouse cells. Genetics. 2002;162:977-85 pubmed
  9. Merker J, Dominska M, Petes T. Patterns of heteroduplex formation associated with the initiation of meiotic recombination in the yeast Saccharomyces cerevisiae. Genetics. 2003;165:47-63 pubmed
  10. Kuzminov A. DNA replication meets genetic exchange: chromosomal damage and its repair by homologous recombination. Proc Natl Acad Sci U S A. 2001;98:8461-8 pubmed
    ..In vitro properties of the eukaryotic recombinases suggest a bigger role for single-strand annealing in the eukaryotic recombinational repair. ..
  11. McCulloch S, Gu L, Li G. Nick-dependent and -independent processing of large DNA loops in human cells. J Biol Chem. 2003;278:50803-9 pubmed
    ..In addition, our data also suggest that an aphidicolin-sensitive DNA polymerase is involved in the excision step of the nick-directed loop repair pathway. ..
  12. Larson E, Nickens D, Drummond J. Construction and characterization of mismatch-containing circular DNA molecules competent for assessment of nick-directed human mismatch repair in vitro. Nucleic Acids Res. 2002;30:E14 pubmed
    ..All repair events were inhibited by a peptide that interacts with proliferating cell nuclear antigen and inhibits both mismatch repair and long-patch replication. ..
  13. Wu S, Culligan K, Lamers M, Hays J. Dissimilar mispair-recognition spectra of Arabidopsis DNA-mismatch-repair proteins MSH2*MSH6 (MutSalpha) and MSH2*MSH7 (MutSgamma). Nucleic Acids Res. 2003;31:6027-34 pubmed
  14. Corrette Bennett S, Mohlman N, Rosado Z, Miret J, Hess P, Parker B, et al. Efficient repair of large DNA loops in Saccharomyces cerevisiae. Nucleic Acids Res. 2001;29:4134-43 pubmed
    ..These observations indicate a robust large loop repair pathway in yeast, distinct from MR and NER, and conserved in mammals. ..
  15. Kearney H, Kirkpatrick D, Gerton J, Petes T. Meiotic recombination involving heterozygous large insertions in Saccharomyces cerevisiae: formation and repair of large, unpaired DNA loops. Genetics. 2001;158:1457-76 pubmed
    ..Although meiotic recombination events in yeast are initiated by double-strand DNA breaks (DSBs), we showed that DSBs occurring within heterozygous insertions do not stimulate interhomologue recombination. ..
  16. Krosky D, Schwarz F, Stivers J. Linear free energy correlations for enzymatic base flipping: how do damaged base pairs facilitate specific recognition?. Biochemistry. 2004;43:4188-95 pubmed
    ..In contrast, the intrinsic instability of other more egregious DNA lesions may contribute significantly to the specificity of other DNA repair enzymes that bind to extrahelical bases. ..
  17. Kaur H, Wengel J, Maiti S. Thermodynamics of DNA-RNA heteroduplex formation: effects of locked nucleic acid nucleotides incorporated into the DNA strand. Biochemistry. 2008;47:1218-27 pubmed publisher
  18. Jia Y, Bi L, Li F, Chen Y, Zhang C, Zhang X. Alpha-shaped DNA loops induced by MutS. Biochem Biophys Res Commun. 2008;372:618-22 pubmed publisher
    ..These data indicate that MutS associates with DNA non-specifically and forms an alpha-loop interaction with the DNA substrate. In this conformation, MutS is able to scan two arms of DNA simultaneously for each MutS dimer formed. ..
  19. Juliano J, Randrianarivelojosia M, Ramarosandratana B, Ariey F, Mwapasa V, Meshnick S. Nonradioactive heteroduplex tracking assay for the detection of minority-variant chloroquine-resistant Plasmodium falciparum in Madagascar. Malar J. 2009;8:47 pubmed publisher
    ..In addition, HTAs for malaria drug resistance alleles are promising tools for the surveillance of anti-malarial resistance. The use of a non-radioactive label allows for the use of HTAs in malaria endemic countries. ..
  20. Michael D, Phillips A, Krupa A, Martin J, Redman J, Altaher A, et al. The human hyaluronan synthase 2 (HAS2) gene and its natural antisense RNA exhibit coordinated expression in the renal proximal tubular epithelial cell. J Biol Chem. 2011;286:19523-32 pubmed publisher
  21. Pande P, Das R, Sheppard C, Kow Y, Basu A. Repair efficiency of (5'S)-8,5'-cyclo-2'-deoxyguanosine and (5'S)-8,5'-cyclo-2'-deoxyadenosine depends on the complementary base. DNA Repair (Amst). 2012;11:926-31 pubmed publisher
    ..This result adds to complexity of human NER, which discriminates the damaged base pairs on the basis of multiple criteria. ..
  22. Jensen L, Barbaux S, Hoess K, Fraterman S, Whitehead A, Mitchell L. The human T locus and spina bifida risk. Hum Genet. 2004;115:475-82 pubmed
    ..The TIVS7 polymorphism or a variant that is in linkage disequilibrium with the TIVS7 polymorphism may, therefore, play a role in T gene expression and influence the risk of spina bifida. ..
  23. Mazina O, Keskin H, Hanamshet K, Storici F, Mazin A. Rad52 Inverse Strand Exchange Drives RNA-Templated DNA Double-Strand Break Repair. Mol Cell. 2017;67:19-29.e3 pubmed publisher
    ..In accord with our in vitro results, our experiments in budding yeast provide evidence that Rad52 inverse strand exchange plays an important role in RNA-templated DSB repair in vivo. ..
  24. Vander Meulen K, Davis J, Foster T, Record M, Butcher S. Thermodynamics and folding pathway of tetraloop receptor-mediated RNA helical packing. J Mol Biol. 2008;384:702-17 pubmed publisher
  25. Li X, Ng M, Wang Y, Zhou T, Chua S, Yuan W, et al. Site-specific self-cleavage of G-quadruplexes formed by human telemetric repeats. Bioorg Med Chem Lett. 2008;18:5576-80 pubmed publisher
    ..Our further studies verify that these reactions are site-specific and undergo hydrolytic pathways. ..
  26. Wang F, Li F, Ganguly M, Marky L, Gold B, Egli M, et al. A bridging water anchors the tethered 5-(3-aminopropyl)-2'-deoxyuridine amine in the DNA major groove proximate to the N+2 C.G base pair: implications for formation of interstrand 5'-GNC-3' cross-links by nitrogen mustards. Biochemistry. 2008;47:7147-57 pubmed publisher
    ..G base pair, facilitating interstrand cross-linking. ..
  27. Cui S, Kim Y, Jin C, Kim S, Rhee M, Kwon O, et al. Synthesis and base pairing properties of DNA-RNA heteroduplex containing 5-hydroxyuridine. BMB Rep. 2009;42:373-9 pubmed
    ..These results suggest that 5-OHU from oxidative damage was mainly influenced by adenine mismatch. ..
  28. Khuu P, Ho P. A rare nucleotide base tautomer in the structure of an asymmetric DNA junction. Biochemistry. 2009;48:7824-32 pubmed publisher
    ..The existence of this unusual base lends credence to and defines a sequence context for the "rare tautomer hypothesis" as a mechanism for inducing transition mutations during DNA replication. ..
  29. Li F, Tian L, Gu L, Li G. Evidence that nucleosomes inhibit mismatch repair in eukaryotic cells. J Biol Chem. 2009;284:33056-61 pubmed publisher
    ..These findings suggest that nucleosomes may inhibit MMR in eukaryotic cells. The implications of these findings for our understanding of eukaryotic MMR are discussed...
  30. Shaw N, Arya D. Recognition of the unique structure of DNA:RNA hybrids. Biochimie. 2008;90:1026-39 pubmed publisher
    ..DNA:RNA hybrids, from their scientific inception to current applications in ligand targeting, are discussed. ..
  31. Gredell J, Dittmer M, Wu M, Chan C, Walton S. Recognition of siRNA asymmetry by TAR RNA binding protein. Biochemistry. 2010;49:3148-55 pubmed publisher
    ..Together, these results demonstrate the importance of the siRNA-TRBP interaction in the selection of the siRNA guide strand in RNAi. ..
  32. Heo S, Cho M, Ku J, Ban C. Steady-state ATPase activity of E. coli MutS modulated by its dissociation from heteroduplex DNA. Biochem Biophys Res Commun. 2007;364:264-9 pubmed
  33. Anderson P, Mecozzi S. Minimum sequence requirements for the binding of paromomycin to the rRNA decoding site A. Biopolymers. 2007;86:95-111 pubmed
    ..The results suggest that MD simulations can supplement in vitro methods as a tool for predicting minimum RNA-binding motifs for both small, rigid ligands, and large, flexible ligands when structural information is available. ..
  34. Pradeepkumar P, Cheruku P, Plashkevych O, Acharya P, Gohil S, Chattopadhyaya J. Synthesis, physicochemical and biochemical studies of 1',2'-oxetane constrained adenosine and guanosine modified oligonucleotides, and their comparison with those of the corresponding cytidine and thymidine analogues. J Am Chem Soc. 2004;126:11484-99 pubmed
  35. Gunnarsson G, Thormar H, Gudmundsson B, Akesson L, Jonsson J. Two-dimensional conformation-dependent electrophoresis (2D-CDE) to separate DNA fragments containing unmatched bulge from complex DNA samples. Nucleic Acids Res. 2004;32:e23 pubmed
    ..This simple and robust method could be used in both analytical and preparative applications involving complex DNA samples. ..
  36. Novopashina D, Totskaya O, Lomzov A, Venyaminova A. 3'-modified oligo (2'-O-methylribonucleotides) as improved probes for hybridization with RNA. Nucleosides Nucleotides Nucleic Acids. 2005;24:527-31 pubmed
  37. Erdeniz N, Dudley S, Gealy R, Jinks Robertson S, Liskay R. Novel PMS1 alleles preferentially affect the repair of primer strand loops during DNA replication. Mol Cell Biol. 2005;25:9221-31 pubmed
    ..In addition, the findings reinforce the current view that during mutation avoidance, MMR is associated with the replication apparatus. ..
  38. Nielsen K, Rasmussen J, Kumar R, Wengel J, Jacobsen J, Petersen M. NMR studies of fully modified locked nucleic acid (LNA) hybrids: solution structure of an LNA:RNA hybrid and characterization of an LNA:DNA hybrid. Bioconjug Chem. 2004;15:449-57 pubmed
    ..The LNA:DNA hybrid structurally resembles an RNA:DNA hybrid as shown by determination of deoxyribose sugar puckers and analysis of NOESY NMR spectra. ..
  39. Sen G, Flora M, Chattopadhyay G, Klinman D, Lees A, Mond J, et al. The critical DNA flanking sequences of a CpG oligodeoxynucleotide, but not the 6 base CpG motif, can be replaced with RNA without quantitative or qualitative changes in Toll-like receptor 9-mediated activity. Cell Immunol. 2004;232:64-74 pubmed
    ..These data further support a potential role for RNA in immunomodulation. ..
  40. Goldfarb T, Alani E. Distinct roles for the Saccharomyces cerevisiae mismatch repair proteins in heteroduplex rejection, mismatch repair and nonhomologous tail removal. Genetics. 2005;169:563-74 pubmed
    ..The involvement of Sgs1p in heteroduplex rejection but not nonhomologous tail removal further illustrates that subsets of MMR proteins collaborate with factors in different DNA repair pathways to maintain genome stability. ..
  41. Huang N, MacKerell A. Atomistic view of base flipping in DNA. Philos Trans A Math Phys Eng Sci. 2004;362:1439-60 pubmed
    ..Other DNA binding proteins that involve distortion of DNA's conformation may use a similar mechanism to that by which M.HhaI facilitates base flipping. ..
  42. Lu A, Clark S, Modrich P. Methyl-directed repair of DNA base-pair mismatches in vitro. 1983. DNA Repair (Amst). 2005;4:134-8; discussion 133, 139 pubmed
  43. Sorokin N, Chechetkin V, Livshits M, Pan kov S, Donnikov M, Gryadunov D, et al. Discrimination between perfect and mismatched duplexes with oligonucleotide gel microchips: role of thermodynamic and kinetic effects during hybridization. J Biomol Struct Dyn. 2005;22:725-34 pubmed
    ..At the same time, these conditions improve the discrimination between perfect and mismatched duplexes more than two-fold. A similar improvement may be obtained using an optimized dissociation procedure. ..
  44. da Silva M, Wilds C, Noronha A, Colvin O, Miller P, Gamcsik M. Accommodation of mispair aligned N3T-ethyl-N3T DNA interstrand cross link. Biochemistry. 2004;43:12549-54 pubmed
    ..Thus, this synthetic DNA is a valuable structural probe to study mechanisms of repair. ..
  45. Todur S, Ashavaid T. Association of Sp1 tandem repeat polymorphism of ALOX5 with coronary artery disease in Indian subjects. Clin Transl Sci. 2012;5:408-11 pubmed publisher
    ..004), HDL(3) -C (p= 0.04), apo A1 (p= 0.011) and sdLDL (p= 0.001). We conclude that this polymorphism influences LDL and HDL subfraction levels and is a risk factor for CAD in our population. Clin Trans Sci 2012; Volume 5: 408-411. ..
  46. Merritt W, Scholdberg T, Nechev L, Harris T, Harris C, Lloyd R, et al. Stereospecific structural perturbations arising from adenine N(6) butadiene triol adducts in duplex DNA. Chem Res Toxicol. 2004;17:1007-19 pubmed
    ..coli DNA polymerases in vitro and may account for their weak mutagenicity [Carmical, J. R., Nechev, L. V., Harris, C. M., Harris, T. M., and Lloyd, R. S. (2000) Environ. Mol. Mutagen. 35, 48-56]. ..
  47. Prakash T, Siwkowski A, Allerson C, Migawa M, Lee S, Gaus H, et al. Antisense oligonucleotides containing conformationally constrained 2',4'-(N-methoxy)aminomethylene and 2',4'-aminooxymethylene and 2'-O,4'-C-aminomethylene bridged nucleoside analogues show improved potency in animal models. J Med Chem. 2010;53:1636-50 pubmed publisher
    ..The data generated in these experiments suggest that N-MeO-amino BNA, N-Me-aminooxy BNA, and 2',4'-BNA(NC)[NMe] are useful modifications for applications in both antisense and other oligonucleotide based drug discovery efforts. ..
  48. Webba da Silva M. Experimental demonstration of T:(G:G:G:G):T hexad and T:A:A:T tetrad alignments within a DNA quadruplex stem. Biochemistry. 2005;44:3754-64 pubmed
  49. Stengel G, Purse B, Wilhelmsson L, Urban M, Kuchta R. Ambivalent incorporation of the fluorescent cytosine analogues tC and tCo by human DNA polymerase alpha and Klenow fragment. Biochemistry. 2009;48:7547-55 pubmed publisher
    ..This finding suggests that the aptitude for ambivalent base pairing is a consequence of the electronic properties of tC(o). ..
  50. Bichenkova E, Savage H, Sardarian A, Douglas K. Target-assembled tandem oligonucleotide systems based on exciplexes for detecting DNA mismatches and single nucleotide polymorphisms. Biochem Biophys Res Commun. 2005;332:956-64 pubmed
    ..Inserts and mismatches can be effectively detected by this exciplex construct giving potential for single nucleotide polymorphism detection. ..
  51. Vo M, Barany G, Rouzina I, Musier Forsyth K. Mechanistic studies of mini-TAR RNA/DNA annealing in the absence and presence of HIV-1 nucleocapsid protein. J Mol Biol. 2006;363:244-61 pubmed
  52. Desai B, Morrison D. Transformation in Streptococcus pneumoniae: formation of eclipse complex in a coiA mutant implicates CoiA in genetic recombination. Mol Microbiol. 2007;63:1107-17 pubmed
  53. Sedletska Y, Fourrier L, Malinge J. Modulation of MutS ATP-dependent functional activities by DNA containing a cisplatin compound lesion (base damage and mismatch). J Mol Biol. 2007;369:27-40 pubmed
    ..We propose that DNA bending could play a role in MutS biochemical modulations induced by a compound lesion and that cisplatin DNA damage signaling by the MMR system could be modulated in a direct mode. ..