Redundant function of DNA ligase 1 and 3 in alternative end-joining during immunoglobulin class switch recombination

DNA ligase IV (Lig4) is essential for nonhomologous end-joining (NHEJ), the major pathway for repairing DNA double-strand breaks in mammalian cells. An ill-defined alternative end-joining (A-EJ) pathway can also mediate end-joining in cells deficient in NHEJ, although A-EJ is kinetically slower and less accurate than NHEJ. Here, we report that either Lig1 or Lig3 can mediate alternative end-joining in Lig4 knockout cells. Cells having only one ligase (Lig1 or nuclear Lig3) are capable of DNA replication and DNA repair after exposure to a wide range of genotoxins. These results demonstrate the remarkable (and unexpected) plasticity of DNA ligases in mammalian cells.