A DNA END-BINDING FACTOR INVOLVED IN DOUBLE-STRAND BREAK REPAIR AND V(D)J RECOMBINATION

We have identified a nuclear factor that binds to double-stranded DNA ends, independently of the structure of the ends. It had equivalent af finities for DNA ends created by sonication or by restriction enzymes leaving 5', 3', or blunt ends but had no detectable affinity for singl e-stranded DNA ends. Since X rays induce DNA double-strand breaks, ext racts from several complementation groups of X-ray-sensitive mammalian cells were tested for this DNA end-binding (DEB) activity. DEB activi ty was deficient in three independently derived cell lines from comple mentation group 5. Furthermore, when the cell lines reverted to X-ray resistance, expression of the DEB factor was restored to normal levels . Previous studies had shown that group 5 cells are defective for both double-strand break repair and V(D)J recombination. The residual V(D) J recombination activity in these cells produces abnormally large dele tions at the sites of DNA joining (F. Pergola, M. Z. Zdzienicka, and M . R. Lieber, Mol. Cell. Biol. 13:3464-3471, 1993, and G. Taccioli, G. Rathbun, E. Oltz, T. Stamato, P. Jeggo, and F. Alt, Science 260:207-21 0, 1993), consistent with deficiency of a factor that protects DNA end s from degradation. Therefore, DEB factor may be involved in a biochem ical pathway common to both double-strand break repair and V(D)J recom bination.