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Article: Systematic yeast synthetic lethal and synthetic dosage lethal screens identify genes required for chromosome segregation

TitleSystematic yeast synthetic lethal and synthetic dosage lethal screens identify genes required for chromosome segregation
Authors
KeywordsChromosome stability
Kinetochore
Synthetic genetic array
Issue Date2005
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2005, v. 102 n. 39, p. 13956-13961 How to Cite?
AbstractAccurate chromosome segregation requires the execution and coordination of many processes during mitosis, including DNA replication, sister chromatid cohesion, and attachment of chromosomes to spindle microtubules via the kinetochore complex. Additional pathways are likely involved because faithful chromosome segregation also requires proteins that are not physically associated with the chromosome. Using kinetochore mutants as a starting point, we have identified genes with roles in chromosome stability by performing genome-wide screens employing synthetic genetic array methodology. Two genetic approaches (a series of synthetic lethal and synthetic dosage lethal screens) isolated 211 nonessential deletion mutants that were unable to tolerate defects in kinetochore function. Although synthetic lethality and synthetic dosage lethality are thought to be based upon similar genetic principles, we found that the majority of interactions associated with these two screens were nonoverlapping. To functionally characterize genes isolated in our screens, a secondary screen was performed to assess defects in chromosome segregation. Genes identified in the secondary screen were enriched for genes with known roles in chromosome segregation. We also uncovered genes with diverse functions, such as RCS1, which encodes an iron transcription factor. RCS1 was one of a small group of genes identified in all three screens, and we used genetic and cell biological assays to confirm that it is required for chromosome stability. Our study shows that systematic genetic screens are a powerful means to discover roles for uncharacterized genes and genes with alternative functions in chromosome maintenance that may not be discovered by using proteomics approaches. © 2005 by The National Academy of Sciences of the USA.
Persistent Identifierhttp://hdl.handle.net/10722/137036
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMeasday, Ven_HK
dc.contributor.authorBaetz, Ken_HK
dc.contributor.authorGuzzo, Jen_HK
dc.contributor.authorYuen, Ken_HK
dc.contributor.authorKwok, Ten_HK
dc.contributor.authorSheikh, Ben_HK
dc.contributor.authorDing, Hen_HK
dc.contributor.authorUeta, Ren_HK
dc.contributor.authorHoac, Ten_HK
dc.contributor.authorCheng, Ben_HK
dc.contributor.authorPot, Ien_HK
dc.contributor.authorTong, Aen_HK
dc.contributor.authorYamaguchiIwai, Yen_HK
dc.contributor.authorBoone, Cen_HK
dc.contributor.authorHieter, Pen_HK
dc.contributor.authorAndrews, Ben_HK
dc.date.accessioned2011-07-29T02:14:47Z-
dc.date.available2011-07-29T02:14:47Z-
dc.date.issued2005en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2005, v. 102 n. 39, p. 13956-13961en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137036-
dc.description.abstractAccurate chromosome segregation requires the execution and coordination of many processes during mitosis, including DNA replication, sister chromatid cohesion, and attachment of chromosomes to spindle microtubules via the kinetochore complex. Additional pathways are likely involved because faithful chromosome segregation also requires proteins that are not physically associated with the chromosome. Using kinetochore mutants as a starting point, we have identified genes with roles in chromosome stability by performing genome-wide screens employing synthetic genetic array methodology. Two genetic approaches (a series of synthetic lethal and synthetic dosage lethal screens) isolated 211 nonessential deletion mutants that were unable to tolerate defects in kinetochore function. Although synthetic lethality and synthetic dosage lethality are thought to be based upon similar genetic principles, we found that the majority of interactions associated with these two screens were nonoverlapping. To functionally characterize genes isolated in our screens, a secondary screen was performed to assess defects in chromosome segregation. Genes identified in the secondary screen were enriched for genes with known roles in chromosome segregation. We also uncovered genes with diverse functions, such as RCS1, which encodes an iron transcription factor. RCS1 was one of a small group of genes identified in all three screens, and we used genetic and cell biological assays to confirm that it is required for chromosome stability. Our study shows that systematic genetic screens are a powerful means to discover roles for uncharacterized genes and genes with alternative functions in chromosome maintenance that may not be discovered by using proteomics approaches. © 2005 by The National Academy of Sciences of the USA.en_HK
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.subjectChromosome stabilityen_HK
dc.subjectKinetochoreen_HK
dc.subjectSynthetic genetic arrayen_HK
dc.titleSystematic yeast synthetic lethal and synthetic dosage lethal screens identify genes required for chromosome segregationen_HK
dc.typeArticleen_HK
dc.identifier.emailYuen, K: kwyyuen@hku.hken_HK
dc.identifier.authorityYuen, K=rp01512en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1073/pnas.0503504102en_HK
dc.identifier.pmid16172405-
dc.identifier.pmcidPMC1236538-
dc.identifier.scopuseid_2-s2.0-25444489018en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-25444489018&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume102en_HK
dc.identifier.issue39en_HK
dc.identifier.spage13956en_HK
dc.identifier.epage13961en_HK
dc.identifier.isiWOS:000232231900045-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridMeasday, V=6602502278en_HK
dc.identifier.scopusauthoridBaetz, K=6602754640en_HK
dc.identifier.scopusauthoridGuzzo, J=8950762600en_HK
dc.identifier.scopusauthoridYuen, K=8841935800en_HK
dc.identifier.scopusauthoridKwok, T=36954282900en_HK
dc.identifier.scopusauthoridSheikh, B=7003370177en_HK
dc.identifier.scopusauthoridDing, H=7402286312en_HK
dc.identifier.scopusauthoridUeta, R=8950763300en_HK
dc.identifier.scopusauthoridHoac, T=8950763400en_HK
dc.identifier.scopusauthoridCheng, B=8950763500en_HK
dc.identifier.scopusauthoridPot, I=6508323450en_HK
dc.identifier.scopusauthoridTong, A=7103351716en_HK
dc.identifier.scopusauthoridYamaguchiIwai, Y=6701865172en_HK
dc.identifier.scopusauthoridBoone, C=7102162162en_HK
dc.identifier.scopusauthoridHieter, P=7006930573en_HK
dc.identifier.scopusauthoridAndrews, B=7202643354en_HK
dc.identifier.issnl0027-8424-

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