MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells.
Nature
; 409(6818): 355-9, 2001 Jan 18.
Article
en En
| MEDLINE
| ID: mdl-11201745
The mitotic checkpoint protein hsMad2 is required to arrest cells in mitosis when chromosomes are unattached to the mitotic spindle. The presence of a single, lagging chromosome is sufficient to activate the checkpoint, producing a delay at the metaphase-anaphase transition until the last spindle attachment is made. Complete loss of the mitotic checkpoint results in embryonic lethality owing to chromosome mis-segregation in various organisms. Whether partial loss of checkpoint control leads to more subtle rates of chromosome instability compatible with cell viability remains unknown. Here we report that deletion of one MAD2 allele results in a defective mitotic checkpoint in both human cancer cells and murine primary embryonic fibroblasts. Checkpoint-defective cells show premature sister-chromatid separation in the presence of spindle inhibitors and an elevated rate of chromosome mis-segregation events in the absence of these agents. Furthermore, Mad2+/- mice develop lung tumours at high rates after long latencies, implicating defects in the mitotic checkpoint in tumorigenesis.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Unión al Calcio
/
Proteínas Fúngicas
/
Proteínas Portadoras
/
Aberraciones Cromosómicas
/
Genes cdc
/
Anafase
/
Neoplasias Pulmonares
Tipo de estudio:
Etiology_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nature
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido