Figure 2.

A. The different stages of canonical NHEJ and AE-J. After the formation of DSBs, the heterodimer Ku70/Ku80 interacts with the ends of the damaged DNA and promotes the recruitment of DNA-PKcs and Artemis. Artemis processes the ends of the DNA to make them compatible for enzymatic ligation by the complex Cernunnos-XLF/XRCC4/Ligase IV complex at the final step. B/ A-EJ: Alternatively, DNA ends that are not protected by Ku70/Ku80 are degraded. It is proposed that a single strand DNA resection reveals complementary microhomologies (2 to 4 nt and more), which can anneal; filling in of the single strand gap or nick complete the end-joining. A-EJ (for Alternative end-joining) is always mutagenic, with deletion at the junctions and frequently (but not systematically) uses microhomologie distant from the DSB. A-EJ is independent on Ku80, Xrcc4, Ligase IV, and is dependent on Parp1, Ligase III. The nuclease activity of MRE11 favors A-EJ.