In:
Stem Cells, Oxford University Press (OUP), Vol. 27, No. 3 ( 2009-03-01), p. 568-576
Abstract:
For mouse embryonic stem (ES) cells, the importance of the S and G2 cell cycle checkpoints for genomic integrity is increased by the absence of the G1 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 G1 arrest after IR but displayed a prominent S-phase delay followed by a G2-phase delay. In contrast, although differentiated EC cells also failed to arrest at G1-phase after IR, they quickly exited S-phase and arrested in G2-phase. In differentiated EC cells, the G2-M-phase cyclin B1/CDC2 complex was upregulated after IR, but the G1-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 G2 checkpoints and a more efficient DNA damage repair system, these mechanisms operate together in the maintenance of genome stability for EC cells.
Type of Medium:
Online Resource
ISSN:
1066-5099
,
1549-4918
DOI:
10.1634/stemcells.2008-0690
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2009
detail.hit.zdb_id:
2030643-X
detail.hit.zdb_id:
1143556-2
detail.hit.zdb_id:
605570-9
SSG:
12
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