Mouse but not human embryonic stem cells are deficient in rejoining of ionizing radiation-induced DNA double-strand breaks
- Bañuelos, Carmen A.
- Banáth, Judit P.
- MacPhail, Susan H.
- Zhao, Jin
- Eaves, Connie J.
- O'Connor, Michael D. (R15206)
- Lansdorp, Peter M.
- Olive, Peggy L.
DOIAbstract
Mouse embryonic stem (mES) cells will give rise to all of the cells of the adult mouse, but they failed to rejoin half of the DNA double-strand breaks (dsb) produced by high doses of ionizing radiation. A deficiency in DNA-PKcs appears to be responsible since mES cells expressed <10% of the level of mouse embryo fibroblasts (MEFs) although Ku70/80 protein levels were higher than MEFs. However, the low level of DNA-PKcs found in wild-type cells appeared sufficient to allow rejoining of dsb after doses <20 Gy even in G1 phase cells. Inhibition of DNA-PKcs with wortmannin and NU7026 still sensitized mES cells to radiation confirming the importance of the residual DNA-PKcs at low doses. In contrast to wild-type cells, mES cells lacking H2AX, a ...
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