Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells
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Author / Producer
Date
2008
Publication Type
Journal Article
ETH Bibliography
no
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OPEN ACCESS
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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.
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Publication status
published
External links
Editor
Book title
Journal / series
Volume
9 (2)
Pages / Article No.
Publisher
BioMed Central
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
Gene Ontology; Mitotic Index; Additional Data File; Mitotic Spindle; Spindle Assembly
Organisational unit
03760 - Hall, Jonathan / Hall, Jonathan