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dc.contributor.author
Au, Wei-Chun
dc.contributor.author
Zhang, Tianyi
dc.contributor.author
Mishra, Prashant K.
dc.contributor.author
Eisenstatt, Jessica R.
dc.contributor.author
Walker, Robert L.
dc.contributor.author
Ocampo, Josefina
dc.contributor.author
Dawson, Anthony
dc.contributor.author
Warren, Jack
dc.contributor.author
Costanzo, Michael
dc.contributor.author
Baryshnikova, Anastasia
dc.contributor.author
Flick, Karin
dc.contributor.author
Clark, David J.
dc.contributor.author
Meltzer, Paul S.
dc.contributor.author
Baker, Richard E.
dc.contributor.author
Myers, Chad
dc.contributor.author
Boone, Charles
dc.contributor.author
Kaiser, Peter
dc.contributor.author
Basrai, Munira A.
dc.date.available
2020-06-24T15:03:09Z
dc.date.issued
2020-02
dc.identifier.citation
Au, Wei-Chun; Zhang, Tianyi; Mishra, Prashant K.; Eisenstatt, Jessica R.; Walker, Robert L.; et al.; Skp, Cullin, F-box (SCF)-Met30 and SCF-Cdc4-Mediated Proteolysis of CENP-A Prevents Mislocalization of CENP-A for Chromosomal Stability in Budding Yeast; Public Library of Science; PLOS Genetics; 16; 2; 2-2020
dc.identifier.uri
http://hdl.handle.net/11336/108091
dc.description.abstract
Restricting the localization of the histone H3 variant CENP-A (Cse4 in yeast, CID in flies) tocentromeres is essential for faithful chromosome segregation. Mislocalization of CENP-Aleads to chromosomal instability (CIN) in yeast, fly and human cells. Overexpression andmislocalization of CENP-A has been observed in many cancers and this correlates withincreased invasiveness and poor prognosis. Yet genes that regulate CENP-A levels andlocalization under physiological conditions have not been defined. In this study we used agenome-wide genetic screen to identify essential genes required for Cse4 homeostasis toprevent its mislocalization for chromosomal stability. We show that two Skp, Cullin, Fbox(SCF) ubiquitin ligases with the evolutionarily conserved F-box proteins Met30 andCdc4 interact and cooperatively regulate proteolysis of endogenous Cse4 and prevent itsmislocalization for faithful chromosome segregation under physiological conditions. Theinteraction of Met30 with Cdc4 is independent of the D domain, which is essential for theirhomodimerization and ubiquitination of other substrates. The requirement for both Cdc4and Met30 for ubiquitination is specifc for Cse4; and a common substrate for Cdc4 andMet30 has not previously been described. Met30 is necessary for the interaction betweenCdc4 and Cse4, and defects in this interaction lead to stabilization and mislocalization ofCse4, which in turn contributes to CIN. We provide the first direct link between Cse4 mislocalizationto defects in kinetochore structure and show that SCF-mediated proteolysis ofPLOS Genetics Cse4 is a major mechanism that prevents stable maintenance of Cse4 at non-centromericregions, thus ensuring faithful chromosome segregation. In summary, we have identifiedessential pathways that regulate cellular levels of endogenous Cse4 and shown that proteolysisof Cse4 by SCF-Met30/Cdc4 prevents mislocalization and CIN in unperturbed cells.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CHROMATIN
dc.subject
CENTROMERE
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CENP-A
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Otros Tópicos Biológicos
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Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Skp, Cullin, F-box (SCF)-Met30 and SCF-Cdc4-Mediated Proteolysis of CENP-A Prevents Mislocalization of CENP-A for Chromosomal Stability in Budding Yeast
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-06-23T15:45:52Z
dc.identifier.eissn
1553-7404
dc.journal.volume
16
dc.journal.number
2
dc.journal.pais
Estados Unidos
dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Au, Wei-Chun. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Zhang, Tianyi. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Mishra, Prashant K.. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Eisenstatt, Jessica R.. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Walker, Robert L.. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Ocampo, Josefina. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
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Fil: Dawson, Anthony. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Warren, Jack. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Costanzo, Michael. University of Toronto; Canadá
dc.description.fil
Fil: Baryshnikova, Anastasia. California Life Company; Estados Unidos
dc.description.fil
Fil: Flick, Karin. University of California; Estados Unidos
dc.description.fil
Fil: Clark, David J.. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Meltzer, Paul S.. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Baker, Richard E.. University of Massachussets; Estados Unidos
dc.description.fil
Fil: Myers, Chad. University of Minnesota; Estados Unidos
dc.description.fil
Fil: Boone, Charles. University of Toronto; Canadá
dc.description.fil
Fil: Kaiser, Peter. University of California; Estados Unidos
dc.description.fil
Fil: Basrai, Munira A.. National Institutes of Health; Estados Unidos
dc.journal.title
PLOS Genetics
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://dx.plos.org/10.1371/journal.pgen.1008597
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pgen.1008597
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