Alternative end-joining pathway(s): Bricolage at DNA breaks

作者：Frit Philippe; Barboule Nadia; Yuan Ying; Gomez Dennis; Calsou Patrick^*

来源：DNA Repair, 2014, 17: 81-97.

DOI：10.1016/j.dnarep.2014.02.007

• DNA repair
• Non-homologous endjoining (NHEJ)
• DNA double-strand breaks (DSBs)
• V(D)J Recombination
• Class-switch recombination
• Telomere

To cope with DNA double strand break (DSB) genotoxicity, cells have evolved two main repair pathways: homologous recombination which uses homologous DNA sequences as repair templates, and non-homologous Ku-dependent end-joining involving direct sealing of DSB ends by DNA ligase IV (Lig4). During the last two decades a third player most commonly named alternative end-joining (A-EJ) has emerged, which is defined as any Ku- or Lig4-independent end-joining process. A-EJ increasingly appears as a highly error-prone bricolage on DSBs and despite expanding exploration, it still escapes full characterization. In the present review, we discuss the mechanism and regulation of A-EJ as well as its biological relevance under physiological and pathological situations, with a particular emphasis on chromosomal instability and cancer. Whether or not it is a genuine DSB repair pathway, A-EJ is emerging as an important cellular process and understanding A-EJ will certainly be a major challenge for the coming years.

• 出版日期2014-5