| First Author | Van Sloun PP | Year | 1999 |
| Journal | Nucleic Acids Res | Volume | 27 |
| Issue | 16 | Pages | 3276-82 |
| PubMed ID | 10454634 | Mgi Jnum | J:56965 |
| Mgi Id | MGI:1342943 | Doi | 10.1093/nar/27.16.3276 |
| Citation | Van Sloun PP, et al. (1999) The role of nucleotide excision repair in protecting embryonic stem cells from genotoxic effects of UV-induced DNA damage. Nucleic Acids Res 27(16):3276-82 |
| abstractText | In this study the role of nucleotide excision repair (NER) in protecting mouse embryonic stem (ES) cells against the genotoxic effects of UV-photolesions was analysed. Repair of cyclobutane pyrimidine dimers (CPD) in transcribed genes could not be detected whereas the removal of (6-4) photoproducts (6-4PP) was incomplete, already reaching its maximum (30%) 4 h after irradiation. Measurements of repair replication revealed a saturation of NER activity at UV doses >5 J/m2 while at a lower dose (2.5 J/m2) the repair kinetics were similar to those in murine embryonic fibroblasts (MEFs). Cytotoxic and mutagenic effects of photolesions were determined in ES cells differing in NER activity. ERCC1-deficient ES cells were hypermutable (10-fold) compared to wild-type cells, indicating that at physiologically relevant doses ES cells efficiently remove photolesions. The effect of the NER deficiency on cytoxicity was only 2-fold. Exposure to high UV doses (10 J/m2) resulted in a rapid and massive induction of apoptosis. Possibly, to avoid the accumulation of mutated cells, ES cells rely on the induction of a strong apoptotic response with a simultaneous shutting down of NER activity. |
