Structures of human exonuclease 1 DNA complexes suggest a unified mechanism for nuclease family.
Cell
; 145(2): 212-23, 2011 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-21496642
ABSTRACT
Human exonuclease 1 (hExo1) plays important roles in DNA repair and recombination processes that maintain genomic integrity. It is a member of the 5' structure-specific nuclease family of exonucleases and endonucleases that includes FEN-1, XPG, and GEN1. We present structures of hExo1 in complex with a DNA substrate, followed by mutagenesis studies, and propose a common mechanism by which this nuclease family recognizes and processes diverse DNA structures. hExo1 induces a sharp bend in the DNA at nicks or gaps. Frayed 5' ends of nicked duplexes resemble flap junctions, unifying the mechanisms of endo- and exonucleolytic processing. Conformational control of a mobile region in the catalytic site suggests a mechanism for allosteric regulation by binding to protein partners. The relative arrangement of substrate binding sites in these enzymes provides an elegant solution to a complex geometrical puzzle of substrate recognition and processing.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Enzimas Reparadoras do DNA
/
Exodesoxirribonucleases
Limite:
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos