Inactivation of the RRB1-Pescadillo pathway involved in ribosome biogenesis induces chromosomal instability

被引：58

作者：

Killian, A ^{[1
]}

Le Meur, N ^{[1
]}

Sesboüe, R ^{[1
]}

Bourguignon, J ^{[1
]}

Bougeard, G ^{[1
]}

Gautherot, J ^{[1
]}

Bastard, C ^{[1
]}

Frébourg, T ^{[1
]}

Flaman, JM ^{[1
]}

机构：

[1] INSERM, U614, IFRMP, Fac Med, F-76183 Rouen, France

来源：

ONCOGENE | 2004年 / 23卷 / 53期

关键词：

cell cycle; chromosomal instability; mitosis; ribosome; yeast;

D O I：

10.1038/sj.onc.1207845

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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, Rp13, 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.

引用

页码：8597 / 8602

页数：6

共 36 条

[1] The spindle checkpoint [J].