Down-regulation of PARP-1, but not of Ku80 or DNA-PKcs, results in higher gene targeting efficiency

The viability of non‐homologous end‐joining (NHEJ)‐defective mice suggests that homologous recombination (HR) might take over its role in DNA repair. To test this hypothesis, we examined gene targeting frequencies (TF) in DNA‐PKcs, Ku80 and poly(ADP‐ribose) polymerase (PARP‐1) nullizygous cells. We observed a 3‐fold TF increase in PARP‐1 knockout embryonic stem (ES) cells, which is consistent with the predicted role of PARP‐1 as a switch between HR and NHEJ. To a lesser extent, such effect could be reproduced upon chemical inhibition of PARP‐1. However, TF was not enhanced in Ku80‐ or DNA‐PKcs‐defective cells. Our study also suggests an unexpected involvement of DNA‐PKcs in HR.