Human FEN-1 can process the 5'-flap DNA of CTG/CAG triplet repeat derived from human genetic diseases by length and sequence dependent manner
Experimental & Molecular Medicine
;
: 313-317, 2002.
Artículo
en Inglés
| WPRIM
| ID: wpr-134585
ABSTRACT
Trinucleotide repeat (TNR) instability can cause a variety of human genetic diseases including myotonic dystrophy and Huntington's disease. Recent genetic data show that instability of the CAG/CTG repeat DNA is dependent on its length and replication origin. In yeast, the RAD27 (human FEN-1 homologue) null mutant has a high expansion frequency at the TNR loci. We demonstrate here that FEN-1 processes the 5'-flap DNA of CTG/CAG repeats, which is dependent on the length in vitro. FEN-1 protein can cleave the 5'-flap DNA containing triplet repeating sequence up to 21 repeats, but the activity decreases with increasing size of flap above 11 repeats. In addition, FEN-1 processing of 5'-flap DNA depends on sequence, which play a role in the replication origin-dependent TNR instability. Interestingly, FEN-1 can cleave the 5'-flap DNA of CTG repeats better than CAG repeats possibly through the flap-structure. Our biochemical data of FEN-1's activity with triplet repeat DNA clearly shows length dependence, and aids our understanding on the mechanism of TNR instability.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
ADN de Cadena Simple
/
Secuencia de Bases
/
Regulación de la Expresión Génica
/
Repeticiones de Trinucleótidos
/
Expansión de Repetición de Trinucleótido
/
Endonucleasas de ADN Solapado
/
Endodesoxirribonucleasas
/
Enfermedades Genéticas Congénitas
/
Conformación de Ácido Nucleico
Límite:
Humanos
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2002
Tipo del documento:
Artículo
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