Alternative end joining is a key mediator of ionizing radiation induced translocations in rodent and human cells - serving as universal backup end joining

Ionizing radiation (IR) induces double strand breaks (DSBs) in cellular DNA, which if not repaired correctly can cause chromosome translocations (CTs) leading to cell death or cancer. Incorrect joining of DNA ends leading to CTs can be catalyzed either by DNA-PKcs-dependent, classical non-homologous end-joining (c-NHEJ), or by an alternative end-joining (alt-EJ) process, functioning as backup to abrogated c-NHEJ or homologous recombination repair, operating with slower kinetics, and generating larger alterations at the junction including CTs. As a result of its fundamental operating properties, alt-EJ is considered crucial to the formation of CTs. A recent study using designer nucleases to induce DSBs and PCR to detect CTs shows a robust, dominant induction of CTs by c-NHEJ in human cells