Inactivation of the RRB1-Pescadillo pathway involved in ribosome biogenesis induces chromosomal instability.
Oncogene
; 23(53): 8597-602, 2004 Nov 11.
Article
em En
| MEDLINE
| ID: mdl-15467761
ABSTRACT
Since chromosomal instability (CIN) is a hallmark of most cancer cells, it is essential to identify genes whose alteration results into this genetic instability. Using a yeast CIN indicator strain, we show that inactivation of the YMR131c/RRB1 gene, which is involved in early ribosome assembly and whose expression is induced when the spindle checkpoint is activated, alters chromosome segregation and blocks mitosis at the metaphase/anaphase transition. We demonstrate that RRB1 interacts with YPH1 (yeast pescadillo homologue 1) and other members of the Yph1 complex, RPL3, ERB1 and ORC6, involved in ribosome biogenesis and DNA replication. Transient depletion of the human homologues GRWD, Pescadillo, Rpl3, Bop1 and Orc6L resulted in an increase of abnormal mitoses with appearance of binucleate or hyperploid cells, of cells with multipolar spindles and of aberrant metaphase plates. If deregulation of proteins involved in ribosome biogenesis, commonly observed in malignant tumors, could contribute to cancer through an aberrant protein synthesis, our study demonstrates that alteration of proteins linking ribosome biogenesis and DNA replication may directly cause CIN.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribossomos
/
Saccharomyces cerevisiae
/
Proteínas Nucleares
/
Proteínas de Saccharomyces cerevisiae
/
Instabilidade Cromossômica
/
Proteínas de Ligação a DNA
/
Mutação
Limite:
Humans
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
França