DNA binding of Xrcc4 protein is associated with V(D)J recombination but not with stimulation of DNA ligase IV activity

Mammalian cells are protected from the effects of DNA double-strand breaks by end-joining repair, Cells lacking the Xrcc4 protein are hypersensitive t o agents that induce DNA double-strand breaks, and are unable to complete V (D)J recombination, The residual repair of broken DNA ends in XRCC4-deficie nt cells requires short sequence homologies, thus possibly implicating Xrcc 4 in end alignment. We show that Xrcc4 binds DNA, and prefers DNA with nick s or broken ends. Xrcc4 also binds to DNA ligase IV and enhances its joinin g activity. This stimulatory effect is shown to occur at the adenylation of the enzyme. DNA binding of Xrcc4 is correlated with its complementation of the V(D)J recombination defects in XRCC4-deficient cells, but is not requi red for stimulation of DNA ligase IV. Thus, the ability of Xrcc4 to bind to DNA suggests functions independent of DNA ligase IV.