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Human classical NHEJ seals double-strand breaks via the XRCC4–DNA ligase IV complex.

The Claim

Classical non-homologous end joining (c-NHEJ) in humans requires DNA ligase IV (LIG4) to seal DNA double-strand breaks.

Verified by Lenz ·

The Short Version

The evidence strongly supports this statement. In humans, canonical/classical NHEJ uses the XRCC4–DNA ligase IV complex to complete ligation of DNA double-strand breaks, and major reviews describe LIG4 as required and specific to c-NHEJ. Reports of other ligases acting in end joining refer to alternative, non-classical pathways rather than c-NHEJ.

Caveats

  • Do not generalize this claim to all end-joining repair: alternative end joining and microhomology-mediated end joining can use other ligases.
  • LIG4 acts in c-NHEJ as part of a complex, especially with XRCC4; the pathway also depends on additional c-NHEJ factors beyond LIG4 alone.
  • 'Requires LIG4' applies to the canonical human pathway as defined in the cited literature, not to backup repair mechanisms activated when c-NHEJ is compromised.

The Receipts

  1. Repair of DNA Double-Strand Breaks by the Non-homologous End Joining Pathway

    PubMed Central (NIH/NLM)

  2. DNA ligase IV guides end-processing choice during nonhomologous end joining

    PubMed Central (Cell Reports)

  3. Repair of Double-Strand Breaks by End Joining

    PubMed Central (Cold Spring Harbor Perspectives in Biology)

  4. Classical non-homologous end-joining and alternative end-joining pathways in mammalian cells

    Nature Reviews Molecular Cell Biology

  5. Non-homologous DNA end joining and alternative pathways to double-strand break repair

    PubMed Central (Nature Communications review via NCBI)

  6. The molecular basis and disease relevance of non-homologous DNA end joining

    PubMed Central (Nature Reviews Molecular Cell Biology via NCBI)

  7. DNA double strand break repair via non-homologous end-joining

    UT Southwestern / Elsevier

  8. Mechanisms of DNA double-strand break repair and chromosomal translocations

    Nature Reviews Molecular Cell Biology

  9. XRCC4:LIG4 ligates DNA DSB ends during NHEJ

    Reactome

  10. Case Report: Hypomorphic Ligase 4 deficiency – a paradigm of continuous disease evolution

    Frontiers in Immunology

+ 6 more sources — see the full list on Lenz

Filed Under

Classical Non-Homologous End JoiningDNA Ligase IV

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