| First Author | Christmann M | Year | 2005 |
| Journal | Oncogene | Volume | 24 |
| Issue | 56 | Pages | 8304-13 |
| PubMed ID | 16103874 | Mgi Jnum | J:104075 |
| Mgi Id | MGI:3611112 | Doi | 10.1038/sj.onc.1208994 |
| Citation | Christmann M, et al. (2005) Fen1 is induced p53 dependently and involved in the recovery from UV-light-induced replication inhibition. Oncogene 24(56):8304-13 |
| abstractText | Mouse embryonic fibroblasts (MEFs) that lack p53 are hypersensitive to the cytotoxic and genotoxic effect of ultraviolet (UV-C) light. They also display a defect in the recovery from UV-C-induced DNA replication inhibition. An enzyme involved in processing stalled DNA replication forks is flap endonuclease 1 (Fen1). Gene expression profiling of UV-C-irradiated MEFs revealed fen1 to be upregulated, which was confirmed by RT-PCR and Western blot experiments. Increased Fen1 levels upon UV-C exposure are due to transcriptional activation, as revealed by inhibitor studies. Fen1 induction was dose- and time-dependent; it occurred on protein level already 3 h after irradiation. Induction of Fen1 by UV-C requires p53 since it was observed in p53 wild-type (wt) but not in p53 null (p53-/-) fibroblasts. Fen1 upregulation paralleled the increase in p53 protein level in replicating wt cells, whereas in nonreplicating cells both Fen1 and p53 were not induced by UV-C. The mouse fen1 promoter was cloned and shown to harbor a p53 consensus sequence to which p53 binds. In cotransfection experiments, p53 stimulated the expression of a fen1 promoter-reporter construct. Transgenic expression of Fen1 in p53 null cells attenuated UV-C light-induced DNA replication inhibition, supporting the hypothesis that Fen1 induction is involved in the recovery of cells from DNA damage. |
