Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends.

Abstract

XRCC4-null mice have a more severe phenotype than KU80-null mice. Here, we address whether this difference in phenotype is connected to nonhomologous end-joining (NHEJ). We used intrachromosomal substrates to monitor NHEJ of two distal double-strand breaks (DSBs) targeted by I-SceI, in living cells. In xrcc4-defective XR-1 cells, a residual but significant end-joining process exists, which primarily uses microhomologies distal from the DSB. However, NHEJ efficiency was strongly reduced in xrcc4-defective XR-1 cells versus complemented cells, contrasting with KU-deficient xrs6 cells, which showed levels of end-joining similar to those of complemented cells. Nevertheless, sequence analysis of the repair junctions indicated that the accuracy of end-joining was strongly affected in both xrcc4-deficient and KU-deficient cells. More specifically, these data showed that the KU80/XRCC4 pathway is conservative and not intrinsically error-prone but can accommodate non-fully complementary ends at the cost of limited mutagenesis.

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@article{GuirouilhBarbat2007DefectsIX, title={Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends.}, author={Jos{\'e}e Guirouilh-Barbat and Emilie Rass and Isabelle Plo and Pascale Bertrand and Bernard S Lopez}, journal={Proceedings of the National Academy of Sciences of the United States of America}, year={2007}, volume={104 52}, pages={20902-7} }