| Autor: |
Colton SL; Institute of Environmental Health Sciences, Karmanos Cancer Research Institute, Wayne State University, Detroit, Michigan 48201, USA., Xu XS, Wang YA, Wang G |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of biological chemistry [J Biol Chem] 2006 Sep 15; Vol. 281 (37), pp. 27117-25. Date of Electronic Publication: 2006 Jul 18. |
| DOI: |
10.1074/jbc.M602826200 |
| Abstrakt: |
DNA damage can lead to either DNA repair with cell survival or to apoptotic cell death. Although the biochemical processes underlying DNA repair and apoptosis have been extensively studied, the mechanisms by which cells determine whether the damage will be repaired or the apoptotic pathway will be activated is largely unknown. We have studied the role of nucleotide excision repair (NER) in cisplatin DNA damage-induced apoptotic cell death using both normal human fibroblasts and NER-defective xeroderma pigmentosum (XP) XPA and XPG cells. The caspase-3 activation experiment demonstrated a greatly increased casapse-3 activation in the NER-defective cells following cisplatin treatment. The flow cytometry experiment revealed an altered cell cycle arrest pattern of the NER-defective cells following cisplatin treatment. The results obtained from the Western blot experiment showed that NER defects resulted in enhanced CHK1 phosphorylation and p21 induction after cisplatin treatment. The cisplatin treatment-induced ATM phosphorylation, however, was attenuated in NER-defective cells. The results obtained from our immunoprecipitation experiment further demonstrated that the ATM protein interacted with the TFIIH basal transcription factor and the XPG protein of the NER pathway. It also showed that a functional XPC protein was required for the association of the ATM protein to genomic DNA. These results suggest that the NER process may prevent the cisplatin treatment-induced apoptosis by activating the ATM protein, and that the presence of the XPC protein is essential for recruiting the ATM protein to the DNA template. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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