Mus81 endonuclease localizes to nucleoli and to regions of DNA damage in human S-phase cells.
Mol Biol Cell
; 14(12): 4826-34, 2003 Dec.
Article
en En
| MEDLINE
| ID: mdl-14638871
ABSTRACT
Mus81 is a highly conserved substrate specific endonuclease. Human Mus81 cleaves Holliday junctions, replication forks, and 3' flap substrates in vitro, suggesting a number of possible in vivo functions. We show here that the abundance of human Mus81 peaks in S-phase and remains high in cells that have completed DNA replication and that Mus81 is a predominantly nuclear protein, with super accumulation in nucleoli. Two RecQ related DNA helicases BLM and WRN that are required for recombination repair in human cells colocalize with Mus81 in nucleoli. However, the nucleolar retention of Mus81 is not dependent on the presence of BLM or WRN, or on ongoing transcription. Mus81 is recruited to localized regions of UV damage in S-phase cells, but not in cells that are blocked from replicating DNA or that have completed replication. The retention of human Mus81 at regions of UV-induced damage specifically in S-phase cells suggest that the enzyme is recruited to the sites at which replication forks encounter damaged DNA. The nucleolar concentration of Mus81 suggests that it is required to repair problems that arise most frequently in the highly repetitive nucleolar DNA. Together these data support a role for Mus81 in recombination repair in higher eukaryotes.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Nucléolo Celular
/
Proteínas de Unión al ADN
/
Reparación del ADN
/
Endonucleasas
Límite:
Humans
Idioma:
En
Revista:
Mol Biol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos