Defining interactions between DNA-PK and ligase IV/XRCC4

Hsin Ling Hsu, Steven M. Yannone, David J. Chen

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Non-homologous end joining (NHEJ) is a major pathway for the repair of DNA double-strand breaks (DSBs) in mammalian cells. DNA-dependent protein kinase (DNA-PK), ligase IV, and XRCC4 are all critical components of the NHEJ repair pathway. DNA-PK is composed of a heterodimeric DNA-binding component, Ku, and a large catalytic subunit, DNA-PKcs. Ligase IV and XRCC4 associate to form a multimeric complex that is also essential for NHEJ. DNA-PK and ligase IV/XRCC4 interact at DNA termini which results in stimulated ligase activity. Here, we define interactions between the components of these two essential complexes, DNA-PK and ligase IV/XRCC4. We find that ligase IV/XRCC4 associates with DNA-PK in a DNA-independent manner. The specific protein-protein interactions that mediate the interaction between these two complexes are further identified. Direct interactions between ligase IV and Ku as well as between XRCC4 and DNA-PKcs are shown. In contrast, binding of ligase IV to DNA-PKcs or XRCC4 to Ku is very weak or non-existent. Our data defines the specific protein pairs involved in the association of DNA-PK and ligase IV/XRCC4, and suggests a molecular mechanism for coordinating the assembly of the DNA repair complex at DNA breaks.

Original languageEnglish (US)
Pages (from-to)225-235
Number of pages11
JournalDNA repair
Volume1
Issue number3
DOIs
StatePublished - Mar 28 2002

Keywords

  • DNA double-strand breaks
  • DNA-PK
  • Ku
  • Ligase IV/XRCC4
  • Non-homologous end joining

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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