V(D)J recombination in mammalian cell mutants defective in DNA double-strand break repair.
V(D)J recombination has been examined in several X-ray-sensitive and double-strand break repair-deficient Chinese hamster cell mutants. Signal joint formation was affected in four mutants (xrs 5, XR-1, V-3, and XR-V9B cells, representing complementation groups 1 through 4, respectively) defective in DNA double-strand break rejoining. Among these four, V-3 and XR-V9B were the most severely affected. Only in V-3 was coding joint formation also affected. Ataxia telangiectasia-like hamster cell mutants (V-E5 and V-G8), which are normal for double-strand break repair but are X ray sensitive, were normal for all aspects of the V(D)J recombination reaction, indicating that X-ray sensitivity is not the common denominator but that the deficiency in double-strand break repair appears to be. The abnormality at the signal joints consisted of an elevated incidence of nucleotide loss from each of the two signal ends. Interestingly, in complementation groups 1 (xrs 5) and 2 (XR-1), signal joint formation was within the normal range under some transfection conditions. This suggests that the affected gene products in these two complementation groups are not catalytic components. Instead, they may be either secondary or stochiometric components involved in the later stages of both the V(D)J recombination reaction and double-strand break repair. The fact that such factors can affect the precision of the signal joint has mechanistic implications for V(D)J recombination.
Pergola
F
F
Department of Pathology, Stanford University School of Medicine, California 94305-5324.
Zdzienicka
M Z
MZ
Lieber
M R
MR
D000818:Animals; D001260:Ataxia Telangiectasia; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000235:genetics* / Q000528:radiation effects; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004260:DNA Repair; D004261:DNA Replication; D005091:Exons; D005816:Genetic Complementation Test; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011995:Recombination, Genetic; D014162:Transfection; D045567:VDJ Recombinases
D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell; D004247:DNA; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases