Structural properties of Friedreich's ataxia d(GAA) repeats.
Biochim Biophys Acta
; 1444(1): 14-24, 1999 Jan 18.
Article
en En
| MEDLINE
| ID: mdl-9931411
ABSTRACT
The expansion of trinucleotide repeat sequences is the underlying cause of a growing number of inherited human disorders. To provide correlations between DNA structure and mechanisms of trinucleotide repeat expansion, we investigated potential secondary structures formed from the complementary strands of d(GAA.TTC)n, a sequence whose expansion is associated with Friedreich's ataxia. In 50 mM NaCl, pH 7.5, d(GAA)15 exhibited a cooperative and reversible decrease in large circular dichroism bands at 248 and 272-274 nm over the temperature range of 5-50 degrees C, providing evidence for a base-paired structure at reduced temperatures. Ultraviolet absorbance melting profiles indicated that the melting temperature (Tm) of d(GAA)15 was 40 degrees C. At 5 degrees C, the central portion of d(GAA)15 was hypersensitive to single-strand-specific P1 nuclease degradation and diethyl pyrocarbonate modification, providing evidence for a hairpin conformation. At temperatures between 25 and 35 degrees C in 50 mM NaCl, the triplet repeat region of d(GAA)15 was uniformly resistant to degradation by P1 nuclease, including the central portion of the sequence. Our results indicate that the structure of d(GAA)15 is a hairpin at 5 degrees C, unknown but partially base-paired at 37 degrees C, and an approximately random coil above 65 degrees C.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ataxia de Friedreich
/
Repeticiones de Trinucleótidos
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
1999
Tipo del documento:
Article
País de afiliación:
Estados Unidos