| Autor: |
Potaman VN; Institute of Biosciences and Technology, Texas A&M University System Health Sciences Center, Houston, TX 77030, USA. vpotaman@ibt.tamushsc.edu, Oussatcheva EA, Lyubchenko YL, Shlyakhtenko LS, Bidichandani SI, Ashizawa T, Sinden RR |
| Jazyk: |
angličtina |
| Zdroj: |
Nucleic acids research [Nucleic Acids Res] 2004 Feb 20; Vol. 32 (3), pp. 1224-31. Date of Electronic Publication: 2004 Feb 20 (Print Publication: 2004). |
| DOI: |
10.1093/nar/gkh274 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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