A link between double-strand break-related repair and V(D)J recombination: the scid mutation.
We show here that mammalian site-specific recombination and DNA-repair pathways share a common factor. The effects of DNA-damaging agents on cell lines derived from mice homozygous for the scid (severe combined immune deficiency) mutation were studied. Surprisingly, all scid cell lines exhibited a profound hypersensitivity to DNA-damaging agents that caused double-strand breaks (x-irradiation and bleomycin) but not to other chemicals that caused single-strand breaks or cross-links. Neutral filter elution assays demonstrated that the x-irradiation hypersensitivity could be correlated with a deficiency in repairing double-strand breaks. These data suggest that the scid gene product is involved in two pathways: DNA repair of random double-strand breaks and the site-specific and lymphoid-restricted variable-(diversity)-joining [V(D)J] DNA rearrangement process. We propose that the scid gene product performs a similar function in both pathways and may be a ubiquitous protein.
Hendrickson
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EA
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Qin
X Q
XQ
Bump
E A
EA
Schatz
D G
DG
Oettinger
M
M
Weaver
D T
DT
D000818:Animals; D000831:Animals, Newborn; D001761:Bleomycin / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D011995:Recombination, Genetic
D001761:Bleomycin