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Article: Impact of G 2 checkpoint defect on centromeric instability

TitleImpact of G 2 checkpoint defect on centromeric instability
Authors
Keywordscentromere
defect
G 2 checkpoint
instability
Issue Date2011
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2011, v. 30 n. 11, p. 1281-1289 How to Cite?
AbstractCentromeric instability is characterized by dynamic formation of centromeric breaks, deletions, isochromosomes and translocations, which are commonly observed in cancer. So far, however, the mechanisms of centromeric instability in cancer cells are still poorly understood. In this study, we tested the hypothesis that G 2 checkpoint defect promotes centromeric instability. Our observations from multiple approaches consistently support this hypothesis. We found that overexpression of cyclin B1, one of the pivotal genes driving G 2 to M phase transition, impaired G 2 checkpoint and promoted the formation of centromeric aberrations in telomerase-immortalized cell lines. Conversely, centromeric instability in cancer cells was ameliorated through reinforcement of G 2 checkpoint by cyclin B1 knockdown. Remarkably, treatment with KU55933 for only 2.5 h, which abrogated G 2 checkpoint, was sufficient to produce centromeric aberrations. Moreover, centromeric aberrations constituted the major form of structural abnormalities in G 2 checkpoint-defective ataxia telangiectasia cells. Statistical analysis showed that the frequencies of centromeric aberrations in G 2 checkpoint-defective cells were always significantly overrepresented compared with random assumption. As there are multiple pathways leading to G 2 checkpoint defect, our finding offers a broad explanation for the common occurrence of centromeric aberrations in cancer cells. © 2011 Macmillan Publishers Limited All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/133574
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong Kong Special Administrative Region, ChinaHKU 7556/06M
Funding Information:

We thank Dr Prochownik, Children's Hospital of Pittsburgh, Pittsburgh, PA, for the kind gift of pApuro-CyclinB1 plasmids, and Department of Pediatrics and Adolescent Medicine, The University of Hong Kong for use of SKY facilities. We also thank Dr JC Tang (Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University) and Professor G Srivastava (Department of Pathology, The University of Hong Kong) for the SLMT-1 cell line, and Dr R Glaser (Department of Medical Microbiology and Immunology, Ohio State University Medical Center) for the HNE-1 cell line; T Chan, PY Cheung, CS Leung, P Mak, J Cheung, A Li and B Lai for technical assistance. This study was supported by a grant from the Research Grants Council of Hong Kong Special Administrative Region, China, Project No. HKU 7556/06M.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorDeng, Wen_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorMak, GWYen_HK
dc.contributor.authorTsang, CMen_HK
dc.contributor.authorChing, YPen_HK
dc.contributor.authorGuan, XYen_HK
dc.contributor.authorHuen, MSYen_HK
dc.contributor.authorCheung, ALMen_HK
dc.date.accessioned2011-05-24T02:11:00Z-
dc.date.available2011-05-24T02:11:00Z-
dc.date.issued2011en_HK
dc.identifier.citationOncogene, 2011, v. 30 n. 11, p. 1281-1289en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/133574-
dc.description.abstractCentromeric instability is characterized by dynamic formation of centromeric breaks, deletions, isochromosomes and translocations, which are commonly observed in cancer. So far, however, the mechanisms of centromeric instability in cancer cells are still poorly understood. In this study, we tested the hypothesis that G 2 checkpoint defect promotes centromeric instability. Our observations from multiple approaches consistently support this hypothesis. We found that overexpression of cyclin B1, one of the pivotal genes driving G 2 to M phase transition, impaired G 2 checkpoint and promoted the formation of centromeric aberrations in telomerase-immortalized cell lines. Conversely, centromeric instability in cancer cells was ameliorated through reinforcement of G 2 checkpoint by cyclin B1 knockdown. Remarkably, treatment with KU55933 for only 2.5 h, which abrogated G 2 checkpoint, was sufficient to produce centromeric aberrations. Moreover, centromeric aberrations constituted the major form of structural abnormalities in G 2 checkpoint-defective ataxia telangiectasia cells. Statistical analysis showed that the frequencies of centromeric aberrations in G 2 checkpoint-defective cells were always significantly overrepresented compared with random assumption. As there are multiple pathways leading to G 2 checkpoint defect, our finding offers a broad explanation for the common occurrence of centromeric aberrations in cancer cells. © 2011 Macmillan Publishers Limited All rights reserved.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectcentromereen_HK
dc.subjectdefecten_HK
dc.subjectG 2 checkpointen_HK
dc.subjectinstabilityen_HK
dc.subject.meshCell Line, Tumor-
dc.subject.meshCentromere - drug effects - metabolism-
dc.subject.meshChromosomal Instability - genetics-
dc.subject.meshCyclin B1 - genetics - metabolism-
dc.subject.meshG2 Phase - genetics-
dc.titleImpact of G 2 checkpoint defect on centromeric instabilityen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0950-9232&volume=30&issue=11&spage=1281&epage=1289&date=2011&atitle=Impact+of+G2+checkpoint+defect+on+centromeric+instability-
dc.identifier.emailDeng, W: wdeng@hkucc.hku.hken_HK
dc.identifier.emailTsao, SW: gswtsao@hku.hken_HK
dc.identifier.emailChing, YP: ypching@hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.emailHuen, MSY: huen.michael@hku.hken_HK
dc.identifier.emailCheung, ALM: lmcheung@hku.hken_HK
dc.identifier.authorityDeng, W=rp01640en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.identifier.authorityChing, YP=rp00469en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.identifier.authorityHuen, MSY=rp01336en_HK
dc.identifier.authorityCheung, ALM=rp00332en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1038/onc.2010.508en_HK
dc.identifier.pmid21057540-
dc.identifier.scopuseid_2-s2.0-79952767681en_HK
dc.identifier.hkuros185089en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79952767681&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume30en_HK
dc.identifier.issue11en_HK
dc.identifier.spage1281en_HK
dc.identifier.epage1289en_HK
dc.identifier.eissn1476-5594-
dc.identifier.isiWOS:000288492100003-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectCentromeric instability in human cells undergoing immortalization: implication for progression of chromosomal instability in carcinogenesis-
dc.identifier.scopusauthoridDeng, W=7202223673en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridMak, GWY=37075049000en_HK
dc.identifier.scopusauthoridTsang, CM=24831236400en_HK
dc.identifier.scopusauthoridChing, YP=7005431277en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK
dc.identifier.scopusauthoridHuen, MSY=23004751500en_HK
dc.identifier.scopusauthoridCheung, ALM=7401806497en_HK
dc.identifier.citeulike8229366-

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