Cloning, Characterization, and Properties of Seven Triplet Repeat DNA Sequences

Ohshima, Keiichi; Kang, Seongman; Larson, Jacquelynn E.; Wells, Robert D.

doi:10.1074/jbc.271.28.16773

Cited by 96 publications

(103 citation statements)

References 69 publications

(70 reference statements)

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“…Furthermore, no rearrangements were observed on analyzing individual colonies obtained from transforming the parental plasmids into E. coli HB101. Likewise, rearrangements were not observed previously in other prior instability studies with triplet repeat inserts in E. coli HB101 (10,16,18,19,39,86,(91)(92)(93). This confirms that the rearrangements were because of an intrinsic property of the pcDNA3.1 shuttle vector that carries the SV40 origin of replication.…”

Section: Resultssupporting

confidence: 64%

“…In case of the tetranucleotide repeats, however, instability refers to both expansions and deletions. Thus, upon initial consideration, our results appear to be similar to the results with the triplet repeat sequences, including CTG⅐CAG, CGG⅐CCG, and GAA⅐TTC, in which orientation II was shown to be more unstable (9,10,16,18,19,21,22,39,52,85,86,95,96). However, the CCTG sequences are genetically unstable in the orientation prone to expand (orientation II) (Fig.…”

Section: Chemical Probe Determinations-d(cagg)supporting

confidence: 72%

“…Previous studies showed a marked effect of orientation of trinucleotide repeats (CTG⅐CAG, CGG⅐CCG, and GAA⅐TTC) with respect to the origin of replication (10,16,18,19,21,39,85,86). Therefore, we studied plasmids carrying the (CCTG⅐CAGG) repeats in both orientations.…”

Section: Resultsmentioning

confidence: 99%

“…Length-dependent Instability of the (CCTG⅐CAGG) n Tetranucleotide Repeats-For CTG⅐CAG, CGG⅐CCG, and GAA⅐TTC trinucleotide repeats, the number of repeat units plays an important role in genetic instability (10,18,21,39,93,94). To evaluate the effect of the length of the (CCTG⅐CAGG) n tetranucleotide repeats (where n ϭ 30, 114, or 200) on the genetic instability, three different lengths of the repeats were studied.…”

Section: Resultsmentioning

confidence: 99%

“…The symbols corresponding to the various probes are shown to the right of the figure. The length of the symbols corresponds to the cleavage intensity as quantitated using ImageQuant version 5. stranded or distorted double-stranded regions in DNA to yield mainly cis-thymine glycols (39,64,65,(72)(73)(74). OsO 4 /piperidine was used to probe d(CCTG) 26 (Fig.…”

Section: Table I Expansions and Deletions Of (Cctg⅐cagg) N Repeatsmentioning

confidence: 99%

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Hairpin Structure-forming Propensity of the (CCTG·CAGG) Tetranucleotide Repeats Contributes to the Genetic Instability Associated with Myotonic Dystrophy Type 2

Dere

Напиерала

Ranum

et al. 2004

Journal of Biological Chemistry

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The genetic instabilities of (CCTG⅐CAGG) n tetranucleotide repeats were investigated to evaluate the molecular mechanisms responsible for the massive expansions found in myotonic dystrophy type 2 (DM2) patients. DM2 is caused by an expansion of the repeat from the normal allele of 26 to as many as 11,000 repeats. Genetic expansions and deletions were monitored in an African green monkey kidney cell culture system (COS-7 cells) as a function of the length (30, 114, or 200 repeats), orientation, or proximity of the repeat tracts to the origin (SV40) of replication. As found for CTG⅐CAG repeats related to DM1, the instabilities were greater for the longer tetranucleotide repeat tracts. Also, the expansions and deletions predominated when cloned in orientation II (CAGG on the leading strand template) rather than I and when cloned proximal rather than distal to the replication origin. Biochemical studies on synthetic d(CAGG) 26 and d(CCTG) 26 as models of unpaired regions of the replication fork revealed that d(CAGG) 26 has a marked propensity to adopt a defined base paired hairpin structure, whereas the complementary d(CCTG) 26 lacks this capacity. The effect of orientation described above differs from all previous results with three triplet repeat sequences (including CTG⅐CAG), which are also involved in the etiologies of other hereditary neurological diseases. However, similar to the triplet repeat sequences, the ability of one of the two strands to form a more stable folded structure, in our case the CAGG strand, explains this unorthodox "reversed" behavior.

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Section: Resultssupporting

confidence: 64%

Section: Chemical Probe Determinations-d(cagg)supporting

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Table I Expansions and Deletions Of (Cctg⅐cagg) N Repeatsmentioning

confidence: 99%

See 3 more Smart Citations

Hairpin Structure-forming Propensity of the (CCTG·CAGG) Tetranucleotide Repeats Contributes to the Genetic Instability Associated with Myotonic Dystrophy Type 2

Dere

Напиерала

Ranum

et al. 2004

Journal of Biological Chemistry

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Molecular Pathogenesis of Friedreich Ataxia

Pandolfo¹

1999

Arch Neurol

102

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Friedreich ataxia, the most common type of inherited ataxia, is itself caused in most cases by a large expansion of an intronic GAA repeat, resulting in decreased expression of the target frataxin gene. The autosomal recessive inheritance of the disease gives this triplet repeat mutation some unique features of natural history and evolution. Frataxin is a mitochondrial protein that has homologues in yeast and even in gram-negative bacteria. Yeast organisms deficient in the frataxin homologue accumulate iron in mitochondria and show increased sensitivity to oxidative stress. This suggests that Friedreich ataxia is caused by mitochondrial dysfunction and free radical toxicity.

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Phenotypic variability in friedreich ataxia: Role of the associated GAA triplet repeat expansion

Montermini

Richeter

Morgan

et al. 1997

Annals of Neurology

251

194

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We studied genotype-phenotype correlations in a group of 100 patients with typical Friedreich ataxia (FRDA), and in three groups of patients with atypical clinical presentations, including 44 Acadian FRDA, 8 late-onset FRDA (LOFA), and 6 FRDA with retained reflexes (FARR). All patients, except 3 with typical FRDA, carried two copies of the FRDA-associated GAA triplet repeat expansion. Overall, the phenotypic spectrum of FRDA appeared to be wider than defined by the currently used diagnostic criteria. Our study indicated the existence of several sources of variability in FRDA. Patients with larger GAA expansions tended to have earlier onset and were more likely to show additional manifestations of the disease. Mitotic instability of the expanded GAA repeats may partially account for the limited degree of correlation between expansion sizes as determined in lymphocytes and clinical parameters. Some clinical variants associated with specific FRDA haplotypes, such as Acadian FRDA and FARR, turned out to be unrelated to expansion sizes. No polymorphism in the frataxin coding sequence could be associated with these clinical variants.

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Cloning, Characterization, and Properties of Seven Triplet Repeat DNA Sequences

Cited by 96 publications

References 69 publications

Hairpin Structure-forming Propensity of the (CCTG·CAGG) Tetranucleotide Repeats Contributes to the Genetic Instability Associated with Myotonic Dystrophy Type 2

Hairpin Structure-forming Propensity of the (CCTG·CAGG) Tetranucleotide Repeats Contributes to the Genetic Instability Associated with Myotonic Dystrophy Type 2

Molecular Pathogenesis of Friedreich Ataxia

Phenotypic variability in friedreich ataxia: Role of the associated GAA triplet repeat expansion

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