Length-dependent structure formation in Friedreich ataxia (GAA)n·(TTC)n repeats at neutral pH

V. N. Potaman, E. A. Oussatcheva, Y. L. Lyubchenko, L. S. Shlyakhtenko, S. I. Bidichandani, T. Ashizawa, R. R. Sinden

Research output: Contribution to journalArticle

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Abstract

More than 15 human genetic diseases have been associated with the expansion of trinucleotide DNA repeats, which may involve the formation of non-duplex DNA structures. The slipped-strand nucleation of duplex DNA within GC-rich trinucleotide repeats may result in the changes of repeat length; however, such a mechanism seems less likely for the AT-rich (GAA)n·(TTC)n repeats. Using two-dimensional agarose gels, chemical probing and atomic force microscopy, we characterized the formation of non-B-DNA structures in the Friedreich ataxia-associated (GAA)n·(TTC n repeats from the FRDA gene that were cloned with flanking genomic sequences into plasmids. For the normal genomic repeat length (n = 9) our data are consistent with the formation of a very stable protonated intramolecular triplex (H-DNA). Its stability at pH 7.4 is likely due to the high proportion of the T·A·T triads which form within the repeats as well as in the immediately adjacent AT-rich sequences with a homopurine· homopyrimidine bias. At the long normal repeat length (n = 23), a family of H-DNAs of slightly different sizes has been detected. At the premutation repeat length (n = 42) and higher negative supercoiling, the formation of a single H-DNA structure becomes less favorable and the data are consistent with the formation of a bi-triplex structure.

Original languageEnglish (US)
Pages (from-to)1224-1231
Number of pages8
JournalNucleic acids research
Volume32
Issue number3
DOIs
StatePublished - Jul 15 2004

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Friedreich Ataxia
DNA Repeat Expansion
DNA
Trinucleotide Repeat Expansion
AT Rich Sequence
Trinucleotide Repeats
Inborn Genetic Diseases
Atomic Force Microscopy
Medical Genetics
Sepharose
Plasmids
Gels
triplex DNA
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Potaman, V. N., Oussatcheva, E. A., Lyubchenko, Y. L., Shlyakhtenko, L. S., Bidichandani, S. I., Ashizawa, T., & Sinden, R. R. (2004). Length-dependent structure formation in Friedreich ataxia (GAA)n·(TTC)n repeats at neutral pH. Nucleic acids research, 32(3), 1224-1231. https://doi.org/10.1093/nar/gkh274

Length-dependent structure formation in Friedreich ataxia (GAA)n·(TTC)n repeats at neutral pH. / Potaman, V. N.; Oussatcheva, E. A.; Lyubchenko, Y. L.; Shlyakhtenko, L. S.; Bidichandani, S. I.; Ashizawa, T.; Sinden, R. R.

In: Nucleic acids research, Vol. 32, No. 3, 15.07.2004, p. 1224-1231.

Research output: Contribution to journalArticle

Potaman, VN, Oussatcheva, EA, Lyubchenko, YL, Shlyakhtenko, LS, Bidichandani, SI, Ashizawa, T & Sinden, RR 2004, 'Length-dependent structure formation in Friedreich ataxia (GAA)n·(TTC)n repeats at neutral pH', Nucleic acids research, vol. 32, no. 3, pp. 1224-1231. https://doi.org/10.1093/nar/gkh274
Potaman VN, Oussatcheva EA, Lyubchenko YL, Shlyakhtenko LS, Bidichandani SI, Ashizawa T et al. Length-dependent structure formation in Friedreich ataxia (GAA)n·(TTC)n repeats at neutral pH. Nucleic acids research. 2004 Jul 15;32(3):1224-1231. https://doi.org/10.1093/nar/gkh274
Potaman, V. N. ; Oussatcheva, E. A. ; Lyubchenko, Y. L. ; Shlyakhtenko, L. S. ; Bidichandani, S. I. ; Ashizawa, T. ; Sinden, R. R. / Length-dependent structure formation in Friedreich ataxia (GAA)n·(TTC)n repeats at neutral pH. In: Nucleic acids research. 2004 ; Vol. 32, No. 3. pp. 1224-1231.
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