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Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells.

Rines, Daniel and Gomez-Ferreira, Maria Ana and Zhou, Yingyao and De Jesus, Paul and Grob, Seanna and Batalov, Sergei and Labow, Mark and Huesken, Dieter and Mickanin, Craig and Hall, Jonathan and Reinhardt, Mischa and Natt, Francois and Lange, Joerg and Sharp, David J and Chanda, Sumit and Caldwell, Jeremy (2008) Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells. Genome Biology, 9 (2). R44. ISSN 1465-6914

Abstract

BACKGROUND: The mitotic spindle is a complex mechanical apparatus required for accurate segregation of sister chromosomes during mitosis. We designed a genetic screen using automated microscopy to discover factors essential for mitotic progression. Using a RNA interference library of 49,164 double-stranded RNAs targeting 23,835 human genes, we performed a loss of function screen to look for small interfering RNAs that arrest cells in metaphase. RESULTS: Here we report the identification of genes that, when suppressed, result in structural defects in the mitotic spindle leading to bent, twisted, monopolar, or multipolar spindles, and cause cell cycle arrest. We further describe a novel analysis methodology for large-scale RNA interference datasets that relies on supervised clustering of these genes based on Gene Ontology, protein families, tissue expression, and protein-protein interactions. CONCLUSION: This approach was utilized to classify functionally the identified genes in discrete mitotic processes. We confirmed the identity for a subset of these genes and examined more closely their mechanical role in spindle architecture.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF may be used
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Date Deposited: 14 Dec 2009 13:51
Last Modified: 31 Jan 2013 01:04
URI: https://oak.novartis.com/id/eprint/897

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