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

  • Shahnaz Masani
    Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824
  • Li Han
    Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824
  • Katheryn Meek
    Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824
  • Kefei Yu
    Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824

説明

<jats:title>Significance</jats:title> <jats:p>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.</jats:p>

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