V(D)J RECOMBINATION - A FUNCTIONAL DEFINITION OF THE JOINING SIGNALS
V(D)J RECOMBINATION - A FUNCTIONAL DEFINITION OF THE JOINING SIGNALS
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DOI：
10.1101/gad.3.7.1053
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发表时间：
1989-07-01
影响因子：
10.5
通讯作者：
GELLERT, M
中科院分区：
文献类型：
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作者：
HESSE, JE;LIEBER, MR;GELLERT, M
两个保守的DNA序列在淋巴分化过程中作为来自V-、（D）-和J-编码区段的免疫球蛋白和T细胞受体的组装中的连接信号。我们研究了V（D）J重组作为连接信号序列的函数。在V（D）J重组中有活性的前B细胞系中，测试了在七聚体-间隔区-九聚体序列中的一个或两个中具有突变的质粒底物的重组。没有信号变体比那些共有形式的连接信号更有效地重组。我们发现七聚体序列是最重要的，特别是，最接近重组交叉位点的三个碱基是至关重要的。九聚体不是严格定义的，并且保持区分共有九聚体序列的五个连续A并不重要。两种类型的信号显示非常相似的序列要求，并且对于间隔子长度> 1bp的变化具有共同点和不耐受性。虽然这两种信号类型共享序列基序，我们没有发现任何证据的重组信号之间的同源性的作用，这表明它们主要作为蛋白质的识别和结合位点。
Two conserved DNA sequences serve as joining signals in the assembly of immunoglobulins and T-cell receptors from V-,(D)-, and J-coding segments during lymphoid differentiation. We have examined V(D)J recombination as a function of joining signal sequence. Plasmid substrates with mutations in one or both of the heptamer-spacer-nonamer sequences were tested for recombination in a pre-B-cell line active in V(D)J recombination. No signal variant recombines more efficiently than those consensus forms of the joining signals. We find the heptamer sequence to be the most important; specifically, the three bases closest to the recombination crossover site are critical. The nonamer is not as rigidly defined, and it is not important to maintain the five consecutive As that distinguish the consensus nonamer sequence both types of signals displays very similar sequence requirements and have in common and intolerance for changes in spacer lenght > 1bp. Although the two signal types share sequence motifs, we find no evidence of a role in recombination for homology between the signals, suggesting that they serve primarily as protein recognition and binding sites.