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 d ouble-strand break repair-deficient Chinese hamster cell mutants. Sign al joint formation was affected in four mutants (xrs 5, XR-1, V-3, and XR-V9B cells, representing complementation groups 1 through 4, respec tively) defective in DNA double-strand break rejoining. Among these fo ur, V-3 and XR-V9B were the most severely affected. Only in V-3 was co ding joint formation also affected. Ataxia telangiectasia-like hamster cell mutants (V-E5 and V-G8), which are normal for double-strand brea k 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 o f 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 transf ection conditions. This suggests that the affected gene products in th ese two complementation groups are not catalytic components. Instead, they may be either secondary or stochiometric components involved in t he later stages of both the V(D)J recombination reaction and double-st rand break repair. The fact that such factors can affect the precision of the signal joint has mechanistic implications for V(D)J recombinat ion.