CHK1-Regulated S-phase Checkpoint Response Reduces Camptothecin Cytotoxity
The cytotoxicity of camptothecin (CPT) is S phase specific and is associated with an inhibition of DNA replication. The relationship between CPT-induced inhibition of DNA replication and CPT cytotoxicity remains unclear. We previously reported that the CPT-induced inhibition reflects an activated S-...
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Veröffentlicht in: | Cell cycle (Georgetown, Tex.) Tex.), 2002-07, Vol.1 (4), p.273-278 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | The cytotoxicity of camptothecin (CPT) is S phase specific and is associated with an inhibition of DNA replication. The relationship between CPT-induced inhibition of DNA replication and CPT cytotoxicity remains unclear. We previously reported that the CPT-induced inhibition reflects an activated S-phase (S) checkpoint response and that this response is mainly regulated by ATR/CHK1 pathway. In this study, by comparing A1-5 and B4, the two transformed rat embryo fibroblasts cell lines, we showed that with higher CHK1 expression, A1-5 cells had a stronger S checkpoint response and were more resistant to CPT-treatment. The data suggested that over-activated CHK1 in CPT-treated A1-5 cells regulated the strong S checkpoint response through the CDC25A/CDK2 pathway. When the CHK-1 regulated strong S checkpoint response was abolished, A1-5 cells became much more sensitive to CPT-induced killing. These data indicated that CHK1 regulated S checkpoint response protected cells from CPT-induced killing.
Key Words:
CHK1, S-phase checkpoint, Camptothecin, DNA damage |
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ISSN: | 1538-4101 1551-4005 |
DOI: | 10.4161/cc.1.4.137 |