Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells
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-st...
Ausführliche Beschreibung
Autor*in: |
Rines, Daniel R [verfasserIn] |
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Englisch |
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2008 |
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Anmerkung: |
© Rines et al.; licensee BioMed Central Ltd. 2008. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( |
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Übergeordnetes Werk: |
Enthalten in: Genome biology - London : BioMed Central, 2000, 9(2008), 2 vom: 26. Feb. |
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Übergeordnetes Werk: |
volume:9 ; year:2008 ; number:2 ; day:26 ; month:02 |
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DOI / URN: |
10.1186/gb-2008-9-2-r44 |
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SPR030002419 |
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520 | |a 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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700 | 1 | |a Batalov, Serge |4 aut | |
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700 | 1 | |a Huesken, Dieter |4 aut | |
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700 | 1 | |a Sharp, David J |4 aut | |
700 | 1 | |a Chanda, Sumit K |4 aut | |
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10.1186/gb-2008-9-2-r44 doi (DE-627)SPR030002419 (SPR)gb-2008-9-2-r44-e DE-627 ger DE-627 rakwb eng Rines, Daniel R verfasserin aut Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Rines et al.; licensee BioMed Central Ltd. 2008. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( 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. Gene Ontology (dpeaa)DE-He213 Mitotic Index (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Mitotic Spindle (dpeaa)DE-He213 Spindle Assembly (dpeaa)DE-He213 Gomez-Ferreria, Maria Ana aut Zhou, Yingyao aut DeJesus, Paul aut Grob, Seanna aut Batalov, Serge aut Labow, Marc aut Huesken, Dieter aut Mickanin, Craig aut Hall, Jonathan aut Reinhardt, Mischa aut Natt, Francois aut Lange, Joerg aut Sharp, David J aut Chanda, Sumit K aut Caldwell, Jeremy S aut Enthalten in Genome biology London : BioMed Central, 2000 9(2008), 2 vom: 26. Feb. (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:9 year:2008 number:2 day:26 month:02 https://dx.doi.org/10.1186/gb-2008-9-2-r44 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2008 2 26 02 |
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10.1186/gb-2008-9-2-r44 doi (DE-627)SPR030002419 (SPR)gb-2008-9-2-r44-e DE-627 ger DE-627 rakwb eng Rines, Daniel R verfasserin aut Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Rines et al.; licensee BioMed Central Ltd. 2008. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( 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. Gene Ontology (dpeaa)DE-He213 Mitotic Index (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Mitotic Spindle (dpeaa)DE-He213 Spindle Assembly (dpeaa)DE-He213 Gomez-Ferreria, Maria Ana aut Zhou, Yingyao aut DeJesus, Paul aut Grob, Seanna aut Batalov, Serge aut Labow, Marc aut Huesken, Dieter aut Mickanin, Craig aut Hall, Jonathan aut Reinhardt, Mischa aut Natt, Francois aut Lange, Joerg aut Sharp, David J aut Chanda, Sumit K aut Caldwell, Jeremy S aut Enthalten in Genome biology London : BioMed Central, 2000 9(2008), 2 vom: 26. Feb. (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:9 year:2008 number:2 day:26 month:02 https://dx.doi.org/10.1186/gb-2008-9-2-r44 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2008 2 26 02 |
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10.1186/gb-2008-9-2-r44 doi (DE-627)SPR030002419 (SPR)gb-2008-9-2-r44-e DE-627 ger DE-627 rakwb eng Rines, Daniel R verfasserin aut Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Rines et al.; licensee BioMed Central Ltd. 2008. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( 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. Gene Ontology (dpeaa)DE-He213 Mitotic Index (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Mitotic Spindle (dpeaa)DE-He213 Spindle Assembly (dpeaa)DE-He213 Gomez-Ferreria, Maria Ana aut Zhou, Yingyao aut DeJesus, Paul aut Grob, Seanna aut Batalov, Serge aut Labow, Marc aut Huesken, Dieter aut Mickanin, Craig aut Hall, Jonathan aut Reinhardt, Mischa aut Natt, Francois aut Lange, Joerg aut Sharp, David J aut Chanda, Sumit K aut Caldwell, Jeremy S aut Enthalten in Genome biology London : BioMed Central, 2000 9(2008), 2 vom: 26. Feb. (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:9 year:2008 number:2 day:26 month:02 https://dx.doi.org/10.1186/gb-2008-9-2-r44 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2008 2 26 02 |
allfieldsGer |
10.1186/gb-2008-9-2-r44 doi (DE-627)SPR030002419 (SPR)gb-2008-9-2-r44-e DE-627 ger DE-627 rakwb eng Rines, Daniel R verfasserin aut Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Rines et al.; licensee BioMed Central Ltd. 2008. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( 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. Gene Ontology (dpeaa)DE-He213 Mitotic Index (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Mitotic Spindle (dpeaa)DE-He213 Spindle Assembly (dpeaa)DE-He213 Gomez-Ferreria, Maria Ana aut Zhou, Yingyao aut DeJesus, Paul aut Grob, Seanna aut Batalov, Serge aut Labow, Marc aut Huesken, Dieter aut Mickanin, Craig aut Hall, Jonathan aut Reinhardt, Mischa aut Natt, Francois aut Lange, Joerg aut Sharp, David J aut Chanda, Sumit K aut Caldwell, Jeremy S aut Enthalten in Genome biology London : BioMed Central, 2000 9(2008), 2 vom: 26. Feb. (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:9 year:2008 number:2 day:26 month:02 https://dx.doi.org/10.1186/gb-2008-9-2-r44 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2008 2 26 02 |
allfieldsSound |
10.1186/gb-2008-9-2-r44 doi (DE-627)SPR030002419 (SPR)gb-2008-9-2-r44-e DE-627 ger DE-627 rakwb eng Rines, Daniel R verfasserin aut Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Rines et al.; licensee BioMed Central Ltd. 2008. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( 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. Gene Ontology (dpeaa)DE-He213 Mitotic Index (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Mitotic Spindle (dpeaa)DE-He213 Spindle Assembly (dpeaa)DE-He213 Gomez-Ferreria, Maria Ana aut Zhou, Yingyao aut DeJesus, Paul aut Grob, Seanna aut Batalov, Serge aut Labow, Marc aut Huesken, Dieter aut Mickanin, Craig aut Hall, Jonathan aut Reinhardt, Mischa aut Natt, Francois aut Lange, Joerg aut Sharp, David J aut Chanda, Sumit K aut Caldwell, Jeremy S aut Enthalten in Genome biology London : BioMed Central, 2000 9(2008), 2 vom: 26. Feb. (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:9 year:2008 number:2 day:26 month:02 https://dx.doi.org/10.1186/gb-2008-9-2-r44 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2008 2 26 02 |
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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">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. 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Rines, Daniel R Gomez-Ferreria, Maria Ana Zhou, Yingyao DeJesus, Paul Grob, Seanna Batalov, Serge Labow, Marc Huesken, Dieter Mickanin, Craig Hall, Jonathan Reinhardt, Mischa Natt, Francois Lange, Joerg Sharp, David J Chanda, Sumit K Caldwell, Jeremy S |
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whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells |
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Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells |
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. © Rines et al.; licensee BioMed Central Ltd. 2008. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( |
abstractGer |
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. © Rines et al.; licensee BioMed Central Ltd. 2008. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( |
abstract_unstemmed |
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. © Rines et al.; licensee BioMed Central Ltd. 2008. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( |
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Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells |
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Gomez-Ferreria, Maria Ana Zhou, Yingyao DeJesus, Paul Grob, Seanna Batalov, Serge Labow, Marc Huesken, Dieter Mickanin, Craig Hall, Jonathan Reinhardt, Mischa Natt, Francois Lange, Joerg Sharp, David J Chanda, Sumit K Caldwell, Jeremy S |
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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">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.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gene Ontology</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Mitotic Index</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Additional Data File</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Mitotic Spindle</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Spindle Assembly</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Gomez-Ferreria, Maria Ana</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhou, Yingyao</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">DeJesus, Paul</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Grob, Seanna</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Batalov, Serge</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Labow, Marc</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Huesken, Dieter</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Mickanin, Craig</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hall, Jonathan</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Reinhardt, Mischa</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Natt, Francois</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Lange, Joerg</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sharp, David J</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Chanda, Sumit K</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Caldwell, Jeremy S</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Genome biology</subfield><subfield code="d">London : BioMed Central, 2000</subfield><subfield code="g">9(2008), 2 vom: 26. 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