Sadofsky M J, Hesse J E, van Gent D C, Gellert M
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, Maryland 20892, USA.
Genes Dev. 1995 Sep 1;9(17):2193-9. doi: 10.1101/gad.9.17.2193.
The RAG-1 protein plays an essential role in V(D)j recombination, but its exact function has not yet been defined. Here we report that a particular mutation in RAG-1 affects recombination by altering the specificity of target sequence usage. Recombination mediated by wild-type RAG-1 is tolerant of a wide range of coding sequences adjacent to the recombination signal. With the mutant RAG-1, recombination is much more demanding; efficient recombination is only found when particular dinucleotides are adjacent to the signal sequence heptamer. The mutant is also more sensitive than wild-type RAG-1 to certain alterations within the signal sequence. We suggest that the RAG-1 protein may interact physically with the target DNA at the coding-signal sequence border.
RAG-1蛋白在V(D)J重组中起着至关重要的作用，但其确切功能尚未明确。在此我们报告，RAG-1中的一种特定突变通过改变靶序列使用的特异性来影响重组。由野生型RAG-1介导的重组对重组信号相邻的多种编码序列具有耐受性。对于突变型RAG-1，重组要求更高；只有当特定的二核苷酸与信号序列七聚体相邻时，才能发现高效重组。该突变体对信号序列内的某些改变也比野生型RAG-1更敏感。我们认为，RAG-1蛋白可能在编码信号序列边界处与靶DNA发生物理相互作用。
