trinucleotide repeats


Summary: Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes.

Top Publications

  1. Kiliszek A, Kierzek R, Krzyzosiak W, Rypniewski W. Atomic resolution structure of CAG RNA repeats: structural insights and implications for the trinucleotide repeat expansion diseases. Nucleic Acids Res. 2010;38:8370-6 pubmed publisher
    ..The CAG repeats and the previously examined CUG structures share a similar pattern of electrostatic charge distribution in the minor groove, which could explain their affinity for the pathogenesis-related MBNL1 protein. ..
  2. Klempíř J, Zidovska J, Stochl J, Ing V, Uhrová T, Roth J. The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease. Mov Disord. 2011;26:125-9 pubmed publisher
    ..We believe that with the current state of knowledge it is not possible to devise a mathematical model for HD onset prediction because too many entirely unknown modifying factors are still involved. ..
  3. Zhang T, Huang J, Gu L, Li G. In vitro repair of DNA hairpins containing various numbers of CAG/CTG trinucleotide repeats. DNA Repair (Amst). 2012;11:201-9 pubmed publisher
    Expansion of CAG/CTG trinucleotide repeats (TNRs) in humans is associated with a number of neurological and neurodegenerative disorders including Huntington's disease...
  4. Sobczak K, Michlewski G, de Mezer M, Kierzek E, Krol J, Olejniczak M, et al. Structural diversity of triplet repeat RNAs. J Biol Chem. 2010;285:12755-64 pubmed publisher
    ..The results of this study provide a comprehensive structural foundation for the functional analysis of triplet repeats in transcripts. ..
  5. Krobitsch S, Kazantsev A. Huntington's disease: From molecular basis to therapeutic advances. Int J Biochem Cell Biol. 2011;43:20-4 pubmed publisher
  6. Degtyareva N, Barber C, Sengupta B, Petty J. Context dependence of trinucleotide repeat structures. Biochemistry. 2010;49:3024-30 pubmed publisher
    ..Thus, an open (CAG)(8) loop and exposed bases in the arms indicate that the strand junction profoundly influences repeated sequences within three-way junctions. ..
  7. Degtyareva N, Barber C, Reddish M, Petty J. Sequence length dictates repeated CAG folding in three-way junctions. Biochemistry. 2011;50:458-65 pubmed publisher
  8. Vallur A, Maizels N. Complementary roles for exonuclease 1 and Flap endonuclease 1 in maintenance of triplet repeats. J Biol Chem. 2010;285:28514-9 pubmed publisher
    b>Trinucleotide repeats can form stable secondary structures that promote genomic instability...
  9. Sicot G, Gourdon G, Gomes Pereira M. Myotonic dystrophy, when simple repeats reveal complex pathogenic entities: new findings and future challenges. Hum Mol Genet. 2011;20:R116-23 pubmed publisher
    ..This review describes some of the recent advances in the understanding of the molecular mechanisms behind DM and other RNA-dominant disorders. ..

More Information


  1. Reddy K, Tam M, Bowater R, Barber M, Tomlinson M, Nichol Edamura K, et al. Determinants of R-loop formation at convergent bidirectionally transcribed trinucleotide repeats. Nucleic Acids Res. 2011;39:1749-62 pubmed publisher
    ..sequences, prokaryotic and mitochondrial replication origins, and disease-associated (CAG)n and (GAA)n trinucleotide repeats. The determinants of trinucleotide R-loop formation are unclear...
  2. Kiliszek A, Kierzek R, Krzyzosiak W, Rypniewski W. Crystal structures of CGG RNA repeats with implications for fragile X-associated tremor ataxia syndrome. Nucleic Acids Res. 2011;39:7308-15 pubmed publisher
    ..CGG helical structures appear relatively stable compared with CAG and CUG tracts. This could be an important factor in the RNA's ligand binding affinity and specificity...
  3. Rosenblatt A, Kumar B, Mo A, Welsh C, Margolis R, Ross C. Age, CAG repeat length, and clinical progression in Huntington's disease. Mov Disord. 2012;27:272-6 pubmed publisher
    ..This suggests that the aging process itself influences clinical outcomes in Huntington's disease. Inconsistent results in prior studies examining CAG repeat length and progression may indeed reflect a lack of age adjustment...
  4. Møllersen L, Rowe A, Larsen E, Rognes T, Klungland A. Continuous and periodic expansion of CAG repeats in Huntington's disease R6/1 mice. PLoS Genet. 2010;6:e1001242 pubmed publisher
    ..Expansion profiles displaying this kind of periodicity in the expansion process have not previously been reported. These in vivo findings imply that mechanistically distinct expansion processes occur in different tissues. ..
  5. Tang W, Dominska M, Greenwell P, Harvanek Z, Lobachev K, Kim H, et al. Friedreich's ataxia (GAA)n•(TTC)n repeats strongly stimulate mitotic crossovers in Saccharomyces cerevisae. PLoS Genet. 2011;7:e1001270 pubmed publisher
    ..These findings indicate that (GAA)(n)•(TTC)(n) tracts can be a potent source of loss of heterozygosity in yeast. ..
  6. Lin Y, Wilson J. Transcription-induced DNA toxicity at trinucleotide repeats: double bubble is trouble. Cell Cycle. 2011;10:611-8 pubmed
    b>Trinucleotide repeats (TNR) are a blessing and a curse...
  7. Degtyareva N, Petty J. Non-B conformations of CAG repeats using 2-aminopurine. Methods Enzymol. 2011;492:213-31 pubmed publisher
    ..Because 2-aminopurine provides both structural and energetic information via fluorescence and also is an innocuous substitution for adenine, significant progress in elucidating the secondary structures of (CAG) repeats will be achieved. ..
  8. Duzdevich D, Li J, Whang J, Takahashi H, Takeyasu K, Dryden D, et al. Unusual structures are present in DNA fragments containing super-long Huntingtin CAG repeats. PLoS ONE. 2011;6:e17119 pubmed publisher
    ..We also raise the possibility that if these structures occur in vivo, they may play a role in the aetiology of CAG repeat diseases such as HD. ..
  9. Volle C, Delaney S. CAG/CTG repeats alter the affinity for the histone core and the positioning of DNA in the nucleosome. Biochemistry. 2012;51:9814-25 pubmed publisher
    b>Trinucleotide repeats (TNRs) occur throughout the genome, and their expansion has been linked to several neurodegenerative disorders, including Huntington's disease...
  10. López Castel A, Cleary J, Pearson C. Repeat instability as the basis for human diseases and as a potential target for therapy. Nat Rev Mol Cell Biol. 2010;11:165-70 pubmed publisher
  11. Tang W, Dominska M, Gawel M, Greenwell P, Petes T. Genomic deletions and point mutations induced in Saccharomyces cerevisiae by the trinucleotide repeats (GAA·TTC) associated with Friedreich's ataxia. DNA Repair (Amst). 2013;12:10-7 pubmed publisher
    Expansion of certain trinucleotide repeats causes several types of human diseases, and such tracts are associated with the formation of deletions and other types of genetic rearrangements in Escherichia coli, yeast, and mammalian cells...
  12. Peprah E, He W, Allen E, Oliver T, Boyne A, Sherman S. Examination of FMR1 transcript and protein levels among 74 premutation carriers. J Hum Genet. 2010;55:66-8 pubmed publisher
    ..Expansion of the CGG trinucleotide repeats to >200 copies (that is, a full mutation) induces methylation of the FMR1 gene, with transcriptional ..
  13. Colak D, Zaninovic N, Cohen M, Rosenwaks Z, Yang W, Gerhardt J, et al. Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X syndrome. Science. 2014;343:1002-5 pubmed publisher
    ..Thus, our data link trinucleotide-repeat expansion to a form of RNA-directed gene silencing mediated by direct interactions of the trinucleotide-repeat RNA and DNA. ..
  14. Skrgatić L, Baldani D, Cerne J, Ferk P, Gersak K. CAG repeat polymorphism in androgen receptor gene is not directly associated with polycystic ovary syndrome but influences serum testosterone levels. J Steroid Biochem Mol Biol. 2012;128:107-12 pubmed publisher
    ..594, P=0.095, P=0.290 and P=0.151, respectively). In conclusion, the AR CAG repeat polymorphism is not a major determinant of PCOS in the Croatian population, but it is a predictor of serum TT level variability in women with PCOS. ..
  15. Hagihara M, He H, Kimura M, Nakatani K. A small molecule regulates hairpin structures in d(CGG) trinucleotide repeats. Bioorg Med Chem Lett. 2012;22:2000-3 pubmed publisher
    Unusual expansion of trinucleotide repeats has been identified as a common mechanism of hereditary neurodegenerative diseases...
  16. Liu C, Chang C, Chern Y, Wang T, Hsieh W, Shen W, et al. Spt4 is selectively required for transcription of extended trinucleotide repeats. Cell. 2012;148:690-701 pubmed publisher
    Lengthy trinucleotide repeats encoding polyglutamine (polyQ) stretches characterize the variant proteins of Huntington's disease and certain other inherited neurological disorders...
  17. Santoro M, Bray S, Warren S. Molecular mechanisms of fragile X syndrome: a twenty-year perspective. Annu Rev Pathol. 2012;7:219-45 pubmed publisher
    ..Studies continue to refine our understanding of FMRP's role in synaptic plasticity and to uncover new functions of this protein, which have illuminated therapeutic approaches for FXS...
  18. Goula A, Pearson C, Della Maria J, Trottier Y, Tomkinson A, Wilson D, et al. The nucleotide sequence, DNA damage location, and protein stoichiometry influence the base excision repair outcome at CAG/CTG repeats. Biochemistry. 2012;51:3919-32 pubmed publisher
    ..Our results show that the BER stoichiometry, nucleotide sequence, and DNA damage position modulate repair outcome and suggest that a suboptimal long-patch BER activity promotes CAG/CTG repeat instability. ..
  19. Wang R, Goodarzi M, Xiong T, Wang D, Azziz R, Zhang H. Negative association between androgen receptor gene CAG repeat polymorphism and polycystic ovary syndrome? A systematic review and meta-analysis. Mol Hum Reprod. 2012;18:498-509 pubmed
    ..In summary, the current systematic review and meta-analysis found that the AR CAG microsatellite repeat polymorphism is unlikely to be a major determining factor in the development of PCOS. ..
  20. Zhang Y, Shishkin A, Nishida Y, Marcinkowski Desmond D, Saini N, Volkov K, et al. Genome-wide screen identifies pathways that govern GAA/TTC repeat fragility and expansions in dividing and nondividing yeast cells. Mol Cell. 2012;48:254-65 pubmed publisher
    ..We propose that similar mechanisms can mediate detrimental metabolism of GAA/TTC tracts in human cells...
  21. Xu M, Gabison J, Liu Y. Trinucleotide repeat deletion via a unique hairpin bypass by DNA polymerase ? and alternate flap cleavage by flap endonuclease 1. Nucleic Acids Res. 2013;41:1684-97 pubmed publisher
    ..Our results provide new insight into the role of BER in modulating genome stability that is associated with human diseases. ..
  22. Chen Y, Hou M. The binding of the Co(II) complex of dimeric chromomycin A3 to GC sites with flanking G:G mismatches. J Inorg Biochem. 2013;121:28-36 pubmed publisher
    Some neurological diseases are correlated with expansion of (CXG)n trinucleotide repeats, which contain many contiguous GpC flanked by mismatched X/X base pair...
  23. Slean M, Reddy K, Wu B, Nichol Edamura K, Kekis M, Nelissen F, et al. Interconverting conformations of slipped-DNA junctions formed by trinucleotide repeats affect repair outcome. Biochemistry. 2013;52:773-85 pubmed publisher
    ..Thus, slipped-junction structure can determine whether repair attempts lead to correction or expansion mutations. ..
  24. Pouladi M, Morton A, Hayden M. Choosing an animal model for the study of Huntington's disease. Nat Rev Neurosci. 2013;14:708-21 pubmed publisher
    ..This should highlight the animal model that is best suited to address a particular question of interest and, ultimately, to expedite the discovery of treatments that will prevent or slow the progression of HD. ..
  25. Datta S, Alam M, Majumdar S, Mehta A, Maiti S, Wadhwa N, et al. Nucleosomal occupancy and CGG repeat expansion: a comparative analysis of triplet repeat region from mouse and human fragile X mental retardation gene 1. Chromosome Res. 2011;19:445-55 pubmed publisher
    ..Our studies demonstrate that flanking DNA sequences can influence repeat instability through modulation of nucleosome occupancy in the region...
  26. McMurray C. Mechanisms of trinucleotide repeat instability during human development. Nat Rev Genet. 2010;11:786-99 pubmed publisher
    ..We need now to connect the dots among human genetics, pathway biochemistry and the appropriate model systems to understand the mechanism of expansion as it occurs in human disease. ..
  27. Rindler P, Bidichandani S. Role of transcript and interplay between transcription and replication in triplet-repeat instability in mammalian cells. Nucleic Acids Res. 2011;39:526-35 pubmed publisher
    ..While both processes may not be sufficient for the initiation of instability, transcription and/or transcript stability seem to further modulate the fork-shift model of triplet-repeat instability. ..
  28. Tong D, Deng J, Sun H, Chen L, Wu X. The relationship between CAG repeat length polymorphism and infertility in Southern Chinese Han women. J Endocrinol Invest. 2010;33:559-63 pubmed publisher
    ..05). These data indicated that (CAG)n repeat polymorphism have some influence, but have not a straight relationship in infertile women with PCOS and with endometriosis in this research population. ..
  29. Panigrahi G, Slean M, Simard J, Gileadi O, Pearson C. Isolated short CTG/CAG DNA slip-outs are repaired efficiently by hMutSbeta, but clustered slip-outs are poorly repaired. Proc Natl Acad Sci U S A. 2010;107:12593-8 pubmed publisher
    Expansions of CTG/CAG trinucleotide repeats, thought to involve slipped DNAs at the repeats, cause numerous diseases including myotonic dystrophy and Huntington's disease...
  30. Figueroa A, Cattie D, Delaney S. Structure of even/odd trinucleotide repeat sequences modulates persistence of non-B conformations and conversion to duplex. Biochemistry. 2011;50:4441-50 pubmed publisher
    Expansion of trinucleotide repeats (TNR) has been implicated in the emergence of neurodegenerative diseases...
  31. Evers M, Tran H, Zalachoras I, Pepers B, Meijer O, den Dunnen J, et al. Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: removal of the CAG containing exon. Neurobiol Dis. 2013;58:49-56 pubmed publisher
    ..These results suggest that exon skipping may be a novel therapeutic approach to reduce polyglutamine-induced toxicity in spinocerebellar ataxia type 3. ..
  32. Zhang T, Liang W, Fang M, Yu J, Ni Y, Li Z. Association of the CAG repeat polymorphisms in androgen receptor gene with polycystic ovary syndrome: a systemic review and meta-analysis. Gene. 2013;524:161-7 pubmed publisher
    ..20, 95% CI 0.11-0.30, p=0.000). This meta-analysis demonstrates no evident association between the CAG length variations in AR gene and PCOS risk, while the CAG length appears to be positively associated with T levels in PCOS patients. ..
  33. Lin Y, Dent S, Wilson J, Wells R, Napierala M. R loops stimulate genetic instability of CTG.CAG repeats. Proc Natl Acad Sci U S A. 2010;107:692-7 pubmed publisher
    ..DNA hybrid. These studies demonstrate that persistent hybrids between the nascent RNA transcript and the template DNA strand at CTG.CAG tracts promote instability of DNA trinucleotide repeats.
  34. Braida C, Stefanatos R, Adam B, Mahajan N, Smeets H, Niel F, et al. Variant CCG and GGC repeats within the CTG expansion dramatically modify mutational dynamics and likely contribute toward unusual symptoms in some myotonic dystrophy type 1 patients. Hum Mol Genet. 2010;19:1399-412 pubmed publisher
    ..The presence of such variant repeats very likely contributes toward the unusual symptoms in the Dutch family and additional symptomatic variation in DM1 via affects on both RNA toxicity and somatic instability. ..
  35. Panigrahi G, Slean M, Simard J, Pearson C. Human mismatch repair protein hMutL? is required to repair short slipped-DNAs of trinucleotide repeats. J Biol Chem. 2012;287:41844-50 pubmed publisher
    ..The joint involvement of hMutS? and hMutL? suggests that repeat instability may be the result of aberrant outcomes of repair attempts. ..
  36. Hu J, Liu J, Yu D, Chu Y, Corey D. Mechanism of allele-selective inhibition of huntingtin expression by duplex RNAs that target CAG repeats: function through the RNAi pathway. Nucleic Acids Res. 2012;40:11270-80 pubmed publisher
  37. Sequeiros J, Ramos E, Cerqueira J, Costa M, Sousa A, Pinto Basto J, et al. Large normal and reduced penetrance alleles in Huntington disease: instability in families and frequency at the laboratory, at the clinic and in the population. Clin Genet. 2010;78:381-7 pubmed publisher
    ..This reinforces the need to understand the genomic context of repeat instability in each family and population. ..
  38. Katsuno M, Tanaka F, Adachi H, Banno H, Suzuki K, Watanabe H, et al. Pathogenesis and therapy of spinal and bulbar muscular atrophy (SBMA). Prog Neurobiol. 2012;99:246-56 pubmed publisher
    ..Pharmacological activation of cellular defense machineries, such as molecular chaperones, ubiquitin-proteasome system, and autophagy, also exerts neuroprotective effects in experimental models of SBMA. ..
  39. Lee J, Zhang J, Su A, Walker J, Wiltshire T, Kang K, et al. A novel approach to investigate tissue-specific trinucleotide repeat instability. BMC Syst Biol. 2010;4:29 pubmed publisher
    ..In addition, our quantitative, genome-wide approach is readily applicable to high-throughput assays and opens the door to widespread applications with the potential to accelerate the discovery of drugs that alter tissue instability. ..
  40. Ofori L, Hoskins J, Nakamori M, Thornton C, Miller B. From dynamic combinatorial 'hit' to lead: in vitro and in vivo activity of compounds targeting the pathogenic RNAs that cause myotonic dystrophy. Nucleic Acids Res. 2012;40:6380-90 pubmed publisher
    ..Most importantly, two compounds are able to partially restore splicing in a mouse model of DM1...
  41. Völker J, Gindikin V, Klump H, Plum G, Breslauer K. Energy landscapes of dynamic ensembles of rolling triplet repeat bulge loops: implications for DNA expansion associated with disease states. J Am Chem Soc. 2012;134:6033-44 pubmed publisher
    ..We propose that such dynamic ensembles and their associated impact on DNA properties influence pathways that lead to DNA expansion. ..
  42. Lee J, Jang S, Benoit N, Hoque M, Califano J, Trink B, et al. Presence of 5-methylcytosine in CpNpG trinucleotides in the human genome. Genomics. 2010;96:67-72 pubmed publisher
  43. Eerola J, Luoma P, Peuralinna T, Scholz S, Paisan Ruiz C, Suomalainen A, et al. POLG1 polyglutamine tract variants associated with Parkinson's disease. Neurosci Lett. 2010;477:1-5 pubmed publisher
    ..Other large case-control studies and analyses on functional differences of POLG1 poly-Q variants are warranted. ..
  44. Nestor C, Monckton D. Correlation of inter-locus polyglutamine toxicity with CAG•CTG triplet repeat expandability and flanking genomic DNA GC content. PLoS ONE. 2011;6:e28260 pubmed publisher
  45. Liu G, Chen X, Bissler J, Sinden R, Leffak M. Replication-dependent instability at (CTG) x (CAG) repeat hairpins in human cells. Nat Chem Biol. 2010;6:652-9 pubmed publisher
    ..Hairpin cleavage by synthetic zinc finger nucleases in these cells has provided the first direct evidence for the formation of hairpin structures during replication in vivo. ..
  46. Jung J, van Jaarsveld M, Shieh S, Xu K, Bonini N. Defining genetic factors that modulate intergenerational CAG repeat instability in Drosophila melanogaster. Genetics. 2011;187:61-71 pubmed publisher
    ..These studies indicate that different aspects of repeat instability are under independent genetic control, and identify CG15262, a protein with a NOT2/3/5 conserved domain, as a modifier of CAG repeat instability in vivo. ..
  47. Aziz N, van Belzen M, Coops I, Belfroid R, Roos R. Parent-of-origin differences of mutant HTT CAG repeat instability in Huntington's disease. Eur J Med Genet. 2011;54:e413-8 pubmed publisher
  48. Kozlowski P, de Mezer M, Krzyzosiak W. Trinucleotide repeats in human genome and exome. Nucleic Acids Res. 2010;38:4027-39 pubmed publisher
    b>Trinucleotide repeats (TNRs) are of interest in genetics because they are used as markers for tracing genotype-phenotype relations and because they are directly involved in numerous human genetic diseases...
  49. Whan V, Hobbs M, McWilliam S, Lynn D, Lutzow Y, Khatkar M, et al. Bovine proteins containing poly-glutamine repeats are often polymorphic and enriched for components of transcriptional regulatory complexes. BMC Genomics. 2010;11:654 pubmed publisher
    ..A distinct subset of these diseases is the result of extreme expansions of polymorphic trinucleotide repeats; typically CAG repeats encoding poly-glutamine (poly-Q) tracts in proteins...
  50. Garcia Lopez A, Monferrer L, Garcia Alcover I, Vicente Crespo M, Alvarez Abril M, Artero R. Genetic and chemical modifiers of a CUG toxicity model in Drosophila. PLoS ONE. 2008;3:e1595 pubmed publisher
    ..These findings provide new insights into the DM1 phenotype, and suggest novel candidates for DM1 treatments. ..
  51. Alluri R, Komandur S, Wagheray A, Chaudhuri J, Sitajayalakshmi -, Meena A, et al. Molecular analysis of CAG repeats at five different spinocerebellar ataxia loci: correlation and alternative explanations for disease pathogenesis. Mol Cells. 2007;24:338-42 pubmed
  52. McConnell R, Middlemist S, Scala C, Strassmann J, Queller D. An unusually low microsatellite mutation rate in Dictyostelium discoideum, an organism with unusually abundant microsatellites. Genetics. 2007;177:1499-507 pubmed
    ..The causal relation may in fact be reversed, with low mutation rates evolving to protect against deleterious fitness effects of mutation at the numerous microsatellites. ..
  53. Grabczyk E, Mancuso M, Sammarco M. A persistent RNA.DNA hybrid formed by transcription of the Friedreich ataxia triplet repeat in live bacteria, and by T7 RNAP in vitro. Nucleic Acids Res. 2007;35:5351-9 pubmed
    ..TTC tracts. RNA.DNA hybrids have a potential role in GAA.TTC tract instability and in the mechanism underlying reduced frataxin mRNA levels in Friedreich Ataxia. ..