V(D)J RECOMBINATION IN MAMMALIAN-CELL MUTANTS DEFECTIVE IN DNA DOUBLE-STRAND BREAK REPAIR

被引:185
作者
PERGOLA, F
ZDZIENICKA, MZ
LIEBER, MR
机构
[1] STANFORD UNIV,MED CTR,SCH MED,DEPT PATHOL,EXPTL ONCOL LAB,STANFORD,CA 94305
[2] LEIDEN UNIV,MGC,DEPT RADIAT GENET & CHEM MUTAGENESIS,SYLVIUS LAB,2333 AL LEIDEN,NETHERLANDS
[3] J A COHEN INST,INTERUNIV RES INST RADIOPATHOL & RADIAT PROTECT,LEIDEN,NETHERLANDS
关键词
D O I
10.1128/MCB.13.6.3464
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:3464 / 3471
页数:8
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