Journal
STEM CELLS
Volume 27, Issue 3, Pages 568-576Publisher
ALPHAMED PRESS
DOI: 10.1634/stemcells.2008-0690
Keywords
Embryonal carcinoma cell; Cell cycle; Checkpoint; Ionizing radiation
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Funding
- General Research Fund of Hong Kong [HKU777708M]
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For mouse embryonic stem (ES) cells, the importance of the S and 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 undifferentiated 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. STEM CELLS 2009; 27: 568-576
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