Cell-type-specific consequences of nucleotide excision repair deficiencies: Embryonic stem cells versus fibroblasts

Genomic Integrity of Mouse Embryonic Stem Cells

“…In agreement with this, upon UV-C treatment, in mES cells only half of photoproducts (cyclobutane pyrimidine dimers and (6-4) photoproducts) are induced (Van Sloun 1999) and at the same time a higher level of cell death is observed compared to somatic cells (de Waard et al 2008). Therefore the same amount of DNA lesions, induces a higher level of cell death in mES cells compared to somatic cells.…”

“…Comparison with mouse embryonic fibroblasts (MEF) revealed a lower cell survival of mES cells after -ray irradiation, inducing oxidative lesions and DNA breaks, after mitomycin C treatment, inducing interstrand crosslinks, mono adducts and oxidative DNA damage and after UV irradiation, inducing DNA lesions with DNA helix distorting properties such as cyclobutane pyrimidine dimers and (6-4) photoproducts (van Sloun et al 1999;de Waard 2008). Also treatment with Nmethyl-N-nitro-N-nitrosoguanidine, that induces a whole range of DNA lesions including O 6 -methylguanine that leads to DNA mispairing, increased cytotoxicity in mES cells compared to Swiss Albino 3T3 mouse fibroblasts (SA 3T3 cells) (Roos et al 2007).…”

DNA Repair in Embryonic Stem Cells

“…Although most DNA repair pathways are more efficient in ESCs than in differentiated cells, for NER it appears to be the opposite (de Waard et al, 2008). While at low doses of UVirradiation, MEFs and ESCs have comparable repair efficiencies, exposure to as little as 5 J/m 2 UVC leads to saturation of the repair capacity in ESCs (Van Sloun et al, 1999).…”

“…The difference between ESCs and differentiated cells might be due to different responses of the transcriptional machinery to photoproducts in the DNA. While RNA synthesis is rapidly blocked in differentiated cells after exposure to UV light, gene transcription is continued for several hours in mESCs, even after irradiation with up to 10J/m 2 (de Waard et al, 2008).…”

“…Genetic deletion of the xpc gene (GGR) further enhanced the number of apoptotic mESCs over the already high number of apoptotic ESCs after UV-irradiation, whereas genetic deletion of the csB gene (TCR) did not affect the rate of cell death of mESCs but significantly elevated their mutation rate after UV-exposure (de Waard et al, 2008). This is in contrast to differentiated cells where UV sensitivity is rather linked to TCR (Conforti et al, 2000;de Waard et al, 2008;Ljungman & Zhang, 1996;Ljungman et al, 1999). The difference between ESCs and differentiated cells might be due to different responses of the transcriptional machinery to photoproducts in the DNA.…”