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Article: Proteasome nuclear activity affects chromosome stability by controlling the turnover of Mms22, a protein important for DNA repair
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TitleProteasome nuclear activity affects chromosome stability by controlling the turnover of Mms22, a protein important for DNA repair
 
AuthorsBenAroya, S1
Agmon, N2
Yuen, K1
Kwok, T1
McManus, K1
Kupiec, M2
Hieter, P1
 
Issue Date2010
 
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/
 
CitationPlos Genetics, 2010, v. 6 n. 2 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pgen.1000852
 
AbstractTo expand the known spectrum of genes that maintain genome stability, we screened a recently released collection of temperature sensitive (Ts) yeast mutants for a chromosome instability (CIN) phenotype. Proteasome subunit genes represented a major functional group, and subsequent analysis demonstrated an evolutionarily conserved role in CIN. Analysis of individual proteasome core and lid subunit mutations showed that the CIN phenotype at semi-permissive temperature is associated with failure of subunit localization to the nucleus. The resultant proteasome dysfunction affects chromosome stability by impairing the kinetics of double strand break (DSB) repair. We show that the DNA repair protein Mms22 is required for DSB repair, and recruited to chromatin in a ubiquitin-dependent manner as a result of DNA damage. Moreover, subsequent proteasome-mediated degradation of Mms22 is necessary and sufficient for cell cycle progression through the G2/M arrest induced by DNA damage. Our results demonstrate for the first time that a double strand break repair protein is a proteasome target, and thus link nuclear proteasomal activity and DSB repair. © 2010 Ben-Aroya et al.
 
ISSN1553-7390
2012 SCImago Journal Rankings: 5.375
 
DOIhttp://dx.doi.org/10.1371/journal.pgen.1000852
 
PubMed Central IDPMC2824753
 
ISI Accession Number IDWOS:000275262700020
Funding AgencyGrant Number
National Institutes of Health (NIH)P01 CA16519
Canadian Institute for Health Research, (CIHR)MOP-38096
NIH roadmapU54 RR020839
Human Frontier Science Program (HFSP)
Killam trust
Israel Science Foundation
US-Israel Bi-national Fund (BSF)
Association for International Cancer Research (AICR)
Israeli Ministry of Science, Culture, and Sport
Funding Information:

PH's research was supported in part by National Institutes of Health (NIH) grant P01 CA16519, Canadian Institute for Health Research, (CIHR) grant MOP-38096, and NIH roadmap grant U54 RR020839. SB-A was supported by a Human Frontier Science Program (HFSP) long-term fellowship and by a research grant from the Killam trust. Work in MK's lab was supported by grants from the Israel Science Foundation, the US-Israel Bi-national Fund (BSF), and the Association for International Cancer Research (AICR). NA was supported by an Eshkol Fellowship from the Israeli Ministry of Science, Culture, and Sport. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorBenAroya, S
 
dc.contributor.authorAgmon, N
 
dc.contributor.authorYuen, K
 
dc.contributor.authorKwok, T
 
dc.contributor.authorMcManus, K
 
dc.contributor.authorKupiec, M
 
dc.contributor.authorHieter, P
 
dc.date.accessioned2011-07-29T02:14:43Z
 
dc.date.available2011-07-29T02:14:43Z
 
dc.date.issued2010
 
dc.description.abstractTo expand the known spectrum of genes that maintain genome stability, we screened a recently released collection of temperature sensitive (Ts) yeast mutants for a chromosome instability (CIN) phenotype. Proteasome subunit genes represented a major functional group, and subsequent analysis demonstrated an evolutionarily conserved role in CIN. Analysis of individual proteasome core and lid subunit mutations showed that the CIN phenotype at semi-permissive temperature is associated with failure of subunit localization to the nucleus. The resultant proteasome dysfunction affects chromosome stability by impairing the kinetics of double strand break (DSB) repair. We show that the DNA repair protein Mms22 is required for DSB repair, and recruited to chromatin in a ubiquitin-dependent manner as a result of DNA damage. Moreover, subsequent proteasome-mediated degradation of Mms22 is necessary and sufficient for cell cycle progression through the G2/M arrest induced by DNA damage. Our results demonstrate for the first time that a double strand break repair protein is a proteasome target, and thus link nuclear proteasomal activity and DSB repair. © 2010 Ben-Aroya et al.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationPlos Genetics, 2010, v. 6 n. 2 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pgen.1000852
 
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pgen.1000852
 
dc.identifier.eissn1553-7404
 
dc.identifier.isiWOS:000275262700020
Funding AgencyGrant Number
National Institutes of Health (NIH)P01 CA16519
Canadian Institute for Health Research, (CIHR)MOP-38096
NIH roadmapU54 RR020839
Human Frontier Science Program (HFSP)
Killam trust
Israel Science Foundation
US-Israel Bi-national Fund (BSF)
Association for International Cancer Research (AICR)
Israeli Ministry of Science, Culture, and Sport
Funding Information:

PH's research was supported in part by National Institutes of Health (NIH) grant P01 CA16519, Canadian Institute for Health Research, (CIHR) grant MOP-38096, and NIH roadmap grant U54 RR020839. SB-A was supported by a Human Frontier Science Program (HFSP) long-term fellowship and by a research grant from the Killam trust. Work in MK's lab was supported by grants from the Israel Science Foundation, the US-Israel Bi-national Fund (BSF), and the Association for International Cancer Research (AICR). NA was supported by an Eshkol Fellowship from the Israeli Ministry of Science, Culture, and Sport. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

 
dc.identifier.issn1553-7390
2012 SCImago Journal Rankings: 5.375
 
dc.identifier.issue2
 
dc.identifier.pmcidPMC2824753
 
dc.identifier.pmid20174551
 
dc.identifier.scopuseid_2-s2.0-77649196564
 
dc.identifier.urihttp://hdl.handle.net/10722/137031
 
dc.identifier.volume6
 
dc.languageeng
 
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofPLoS Genetics
 
dc.relation.referencesReferences in Scopus
 
dc.titleProteasome nuclear activity affects chromosome stability by controlling the turnover of Mms22, a protein important for DNA repair
 
dc.typeArticle
 
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Author Affiliations
  1. Michael Smith Laboratories
  2. Tel Aviv University