Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2007

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

Résumé

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.

Dates et versions

hal-03048190 , version 1 (09-12-2020)

Identifiants

Citer

Josée Guirouilh-Barbat, Emilie Rass, Isabelle Plo, Pascale Bertrand, Bernard S. Lopez. Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104 (52), pp.20902-20907. ⟨10.1073/pnas.0708541104⟩. ⟨hal-03048190⟩

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