A winged helix domain in human MUS81 binds DNA and modulates the endonuclease activity of MUS81 complexes.
Nucleic Acids Res
; 41(21): 9741-52, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-23982516
ABSTRACT
The MUS81-EME1 endonuclease maintains metazoan genomic integrity by cleaving branched DNA structures that arise during the resolution of recombination intermediates. In humans, MUS81 also forms a poorly characterized complex with EME2. Here, we identify and determine the structure of a winged helix (WH) domain from human MUS81, which binds DNA. WH domain mutations greatly reduce binding of the isolated domain to DNA and impact on incision activity of MUS81-EME1/EME2 complexes. Deletion of the WH domain reduces the endonuclease activity of both MUS81-EME1 and MUS81-EME2 complexes, and incisions made by MUS81-EME2 are made closer to the junction on substrates containing a downstream duplex, such as fork structures and nicked Holliday junctions. WH domain mutation or deletion in Schizosaccharomyces pombe phenocopies the DNA-damage sensitivity of strains deleted for mus81. Our results indicate an important role for the WH domain in both yeast and human MUS81 complexes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação a DNA
/
Endodesoxirribonucleases
/
Endonucleases
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Reino Unido