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

DNA Repair (Amst). 2014 May;17:81-97. doi: 10.1016/j.dnarep.2014.02.007. Epub 2014 Mar 6.

Abstract

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.

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

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, Nuclear / metabolism
  • Chromosomal Instability
  • DNA Breaks, Double-Stranded*
  • DNA End-Joining Repair*
  • DNA Ligases / metabolism
  • DNA Repair Enzymes / metabolism*
  • DNA-Binding Proteins / metabolism
  • Humans
  • Ku Autoantigen
  • Models, Genetic
  • Neoplasms / genetics*

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Xrcc6 protein, human
  • Ku Autoantigen
  • DNA Ligases
  • DNA Repair Enzymes