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Article: DNA damage mediated s and g 2 checkpoints in human embryonal carcinoma cells

TitleDNA damage mediated s and g 2 checkpoints in human embryonal carcinoma cells
Authors
KeywordsCell cycle
Checkpoint
Embryonal carcinoma cell
Ionizing radiation
Issue Date2009
PublisherAlphaMed Press, Inc. The Journal's web site is located at http://www.stemcells.com
Citation
Stem Cells, 2009, v. 27 n. 3, p. 568-576 How to Cite?
AbstractFor mouse embryonic stem (ES) cells, the importance of the Sand G 2 cell cycle checkpoints for genomic integrity is increased by the absence of the G 1 checkpoint. We have investigated ionizing radiation (IR)-mediated cell cycle checkpoints in undifferentiated and retinoic acid-differentiated human embryonal carcinoma (EC) cells. Like mouse ES cells, human EC cells did not undergo G 1 arrest after IR but displayed a prominent S-phase delay followed by a G 2-phase delay. In contrast, although differentiated EC cells also failed to arrest at G 1-phase after IR, they quickly exited S-phase and arrested in G 2-phase. In differentiated EC cells, the G 2-M-phase cyclin B1/CDC2 complex was upregulated after IR, but the G 1-S-phase cyclin E and the cyclin E/ CDK2 complex were expressed at constitutively low levels, which could be an important factor distinguishing DNA damage responses between undifferentiated and differentiated EC cells. S-phase arrest and expression of p21 could be inhibited by 7-hydroxystaurosporine, suggesting that the ataxia-telangiectasia and Rad-3-related-checkpoint kinase 1 (ATR-CHK1), and p21 pathways might play a role in the IR-mediated S-phase checkpoint in EC cells. IR-mediated phosphorylation of ataxia-telangiectasia mutated, (CHK1), and checkpoint kinase 2 were distinctly higher in undiffer- entiated EC cells compared with differentiated EC cells. Combined with the prominent S and G 2 checkpoints and a more efficient DNA damage repair system, these mechanisms operate together in the maintenance of genome stability for EC cells. ©AlphaMed Press.
Persistent Identifierhttp://hdl.handle.net/10722/59897
ISSN
2015 Impact Factor: 5.902
2015 SCImago Journal Rankings: 3.438
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
General Research Fund of Hong KongHKU777708M
Funding Information:

The authors thank Prof. S. T. Fan for the. nancial support of this study. This work was also supported by General Research Fund of Hong Kong to X. Q. Wang (HKU777708M).

References

 

DC FieldValueLanguage
dc.contributor.authorWang, Xen_HK
dc.contributor.authorLui, VCHen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorPing, LUen_HK
dc.contributor.authorPoon, RYCen_HK
dc.date.accessioned2010-05-31T03:59:41Z-
dc.date.available2010-05-31T03:59:41Z-
dc.date.issued2009en_HK
dc.identifier.citationStem Cells, 2009, v. 27 n. 3, p. 568-576en_HK
dc.identifier.issn1066-5099en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59897-
dc.description.abstractFor mouse embryonic stem (ES) cells, the importance of the Sand G 2 cell cycle checkpoints for genomic integrity is increased by the absence of the G 1 checkpoint. We have investigated ionizing radiation (IR)-mediated cell cycle checkpoints in undifferentiated and retinoic acid-differentiated human embryonal carcinoma (EC) cells. Like mouse ES cells, human EC cells did not undergo G 1 arrest after IR but displayed a prominent S-phase delay followed by a G 2-phase delay. In contrast, although differentiated EC cells also failed to arrest at G 1-phase after IR, they quickly exited S-phase and arrested in G 2-phase. In differentiated EC cells, the G 2-M-phase cyclin B1/CDC2 complex was upregulated after IR, but the G 1-S-phase cyclin E and the cyclin E/ CDK2 complex were expressed at constitutively low levels, which could be an important factor distinguishing DNA damage responses between undifferentiated and differentiated EC cells. S-phase arrest and expression of p21 could be inhibited by 7-hydroxystaurosporine, suggesting that the ataxia-telangiectasia and Rad-3-related-checkpoint kinase 1 (ATR-CHK1), and p21 pathways might play a role in the IR-mediated S-phase checkpoint in EC cells. IR-mediated phosphorylation of ataxia-telangiectasia mutated, (CHK1), and checkpoint kinase 2 were distinctly higher in undiffer- entiated EC cells compared with differentiated EC cells. Combined with the prominent S and G 2 checkpoints and a more efficient DNA damage repair system, these mechanisms operate together in the maintenance of genome stability for EC cells. ©AlphaMed Press.en_HK
dc.languageengen_HK
dc.publisherAlphaMed Press, Inc. The Journal's web site is located at http://www.stemcells.comen_HK
dc.relation.ispartofStem Cellsen_HK
dc.subjectCell cycleen_HK
dc.subjectCheckpointen_HK
dc.subjectEmbryonal carcinoma cellen_HK
dc.subjectIonizing radiationen_HK
dc.subject.meshBlotting, Western-
dc.subject.meshDNA Damage - genetics - physiology-
dc.subject.meshEmbryonal Carcinoma Stem Cells - cytology - metabolism-
dc.subject.meshG2 Phase - genetics-
dc.subject.meshS Phase - genetics-
dc.titleDNA damage mediated s and g 2 checkpoints in human embryonal carcinoma cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1066-5099&volume=27&spage=568&epage=576&date=2009&atitle=DNA+damage-mediated+S+and+G2+checkpoint+in+human+embryonal+carcinoma+cellsen_HK
dc.identifier.emailWang, X: xqwang@hkucc.hku.hken_HK
dc.identifier.emailLui, VCH: vchlui@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.authorityWang, X=rp00507en_HK
dc.identifier.authorityLui, VCH=rp00363en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1634/stemcells.2008-0690en_HK
dc.identifier.pmid19259937en_HK
dc.identifier.pmcidPMC2798066-
dc.identifier.scopuseid_2-s2.0-65249093701en_HK
dc.identifier.hkuros161273en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-65249093701&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume27en_HK
dc.identifier.issue3en_HK
dc.identifier.spage568en_HK
dc.identifier.epage576en_HK
dc.identifier.eissn1549-4918-
dc.identifier.isiWOS:000264706900009-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWang, X=17343159900en_HK
dc.identifier.scopusauthoridLui, VCH=7004231344en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridPing, LU=26638415400en_HK
dc.identifier.scopusauthoridPoon, RYC=7103097213en_HK

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