Defining interactions between DNA-PK and ligase IV/XRCC4

Journal Article · Tue Apr 10 04:00:00 EDT 2001 · DNA Repair

OSTI ID:860724

Hsu, Hsin-Ling; Chen, David J

Non-homologous end joining (NHEJ) is a major pathway for the repair of DNA double-strand breaks 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 physical interactions between ligase IV and Ku as well as between XRCC4 and DNA-PKcs are shown. No direct interactions are observed between ligase IV and DNA-PKcs or between XRCC4 and Ku. 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.

• Research Organization: Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
• Sponsoring Organization: USDOE Director, Office of Science. Office of Biological andEnvironmental Research. Life Sciences Division; National Institutes ofHealth
• DOE Contract Number: AC02-05CH11231
• OSTI ID: 860724
• Report Number(s): LBNL--47730
• Journal Information: DNA Repair, Journal Name: DNA Repair Journal Issue: 3 Vol. 1
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BIOLOGICAL PATHWAYS
DNA
DNA REPAIR
LIGASES
PHOSPHOTRANSFERASES
PROTEINS
REPAIR