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Article: Proteasome nuclear activity affects chromosome stability by controlling the turnover of Mms22, a protein important for DNA repair

TitleProteasome nuclear activity affects chromosome stability by controlling the turnover of Mms22, a protein important for DNA repair
Authors
Issue Date2010
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/
Citation
Plos Genetics, 2010, v. 6 n. 2 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/137031
ISSN
2014 Impact Factor: 7.528
PubMed Central ID
ISI Accession Number ID
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.

References

 

DC FieldValueLanguage
dc.contributor.authorBenAroya, Sen_HK
dc.contributor.authorAgmon, Nen_HK
dc.contributor.authorYuen, Ken_HK
dc.contributor.authorKwok, Ten_HK
dc.contributor.authorMcManus, Ken_HK
dc.contributor.authorKupiec, Men_HK
dc.contributor.authorHieter, Pen_HK
dc.date.accessioned2011-07-29T02:14:43Z-
dc.date.available2011-07-29T02:14:43Z-
dc.date.issued2010en_HK
dc.identifier.citationPlos Genetics, 2010, v. 6 n. 2en_HK
dc.identifier.issn1553-7390en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137031-
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.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/en_HK
dc.relation.ispartofPLoS Geneticsen_HK
dc.titleProteasome nuclear activity affects chromosome stability by controlling the turnover of Mms22, a protein important for DNA repairen_HK
dc.typeArticleen_HK
dc.identifier.emailYuen, K: kwyyuen@hku.hken_HK
dc.identifier.authorityYuen, K=rp01512en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pgen.1000852en_HK
dc.identifier.pmid20174551en_HK
dc.identifier.pmcidPMC2824753-
dc.identifier.scopuseid_2-s2.0-77649196564en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77649196564&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue2en_HK
dc.identifier.eissn1553-7404-
dc.identifier.isiWOS:000275262700020-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridBenAroya, S=7801623784en_HK
dc.identifier.scopusauthoridAgmon, N=8676512000en_HK
dc.identifier.scopusauthoridYuen, K=8841935800en_HK
dc.identifier.scopusauthoridKwok, T=36954282900en_HK
dc.identifier.scopusauthoridMcManus, K=7005089031en_HK
dc.identifier.scopusauthoridKupiec, M=7006462515en_HK
dc.identifier.scopusauthoridHieter, P=7006930573en_HK

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