RNaseH2 mutants that cause Aicardi-Goutieres syndrome are active nucleases.
J Mol Med (Berl)
; 87(1): 25-30, 2009 Jan.
Article
en En
| MEDLINE
| ID: mdl-19034401
ABSTRACT
Mutations in the genes encoding the RNaseH2 and TREX1 nucleases have been identified in patients with Aicardi-Goutieres syndrome (AGS). To determine if the AGS RNaseH2 mutations result in the loss of nuclease activity, the human wild-type RNaseH2 and four mutant complexes that constitute the majority of mutations identified in AGS patients have been prepared and tested for ribonuclease H activity. The heterotrimeric structures of the mutant RNaseH2 complexes are intact. Furthermore, the ribonuclease H activities of the mutant complexes are indistinguishable from the wild-type enzyme with the exception of the RNaseH2 subunit A (Gly37Ser) mutant, which exhibits some evidence of altered nuclease specificity. These data indicate that the mechanism of RNaseH2 dysfunction in AGS cannot be simply explained by loss of ribonuclease H activity and points to a more complex mechanism perhaps mediated through altered interactions with as yet identified nucleic acids or protein partners.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ribonucleasa H
/
Mutación Missense
/
Encefalopatías Metabólicas Innatas
Límite:
Humans
Idioma:
En
Revista:
J Mol Med (Berl)
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos