Menage à trois: double strand break repair, V(D)J recombination and DNA-PK.
All organisms possess mechanisms to repair double strand breaks (dsbs) generated in their DNA by damaging agents. Site-specific dsbs are also introduced during V(D)J recombination. Four complementation groups of radiosensitive rodent mutants are defective in the repair of dsbs, and are unable to carry out V(D)J recombination effectively. The immune defect in Severe Combined Immunodeficient (scid) mice also results from an inability to undergo effective V(D)J recombination, and scid cell lines display a repair defect and belong to one of these complementation groups. These findings indicate a mechanistic overlap between the processes of DNA repair and V(D)J recombination. Recently, two of the genes defined by these complementation groups have been identified and shown to encode components of DNA-dependent protein kinase (DNA-PK). We review here the three fields which have become linked by these findings, and discuss the involvement of DNA-PK in dsb rejoining and in V(D)J recombination.
Jeggo
P A
PA
MRC Cell Mutation Unit, University of Sussex, Brighton, UK.
Taccioli
G E
GE
Jackson
S P
SP
D000818:Animals; D005075:Biological Evolution; D004249:DNA Damage; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D016513:Mice, SCID; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011995:Recombination, Genetic
D004268:DNA-Binding Proteins; D007135:Immunoglobulin Variable Region; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases