Joining-deficient RAG1 mutants block V(D)J recombination in vivo and hairpin opening in vitro

被引:57
作者
Schultz, HY
Landree, MA
Qiu, JX
Kale, SB
Roth, DB [1 ]
机构
[1] Baylor Coll Med, Interdisciplinary Program Cell & Mol Biol, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA
[3] Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA
关键词
D O I
10.1016/S1097-2765(01)00155-1
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
The RAG proteins cleave at V(D)J recombination signal sequences then form a postcleavage complex with the broken ends. The role of this complex in end processing and joining, if any, is undefined. We have identified two RAG1 mutants proficient for DNA cleavage but severely defective for coding and signal joint formation, providing direct evidence that RAG1 is critical for joining in vivo and strongly suggesting that the postcleavage complex is important in end joining. We have also identified a RAG1 mutant that is severely defective for both hairpin opening in vitro and coding joint formation in vivo. These data suggest that the hairpin opening activity of the RAG proteins plays an important physiological role in V(D)J recombination.
引用
收藏
页码:65 / 75
页数:11
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