THE BASIS FOR THE MECHANISTIC BIAS FOR DELETIONAL OVER INVERSIONAL V(D)J RECOMBINATION
THE BASIS FOR THE MECHANISTIC BIAS FOR DELETIONAL OVER INVERSIONAL V(D)J RECOMBINATION
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DOI：
10.1101/gad.6.8.1553
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发表时间：
1992-08-01
影响因子：
10.5
通讯作者：
LIEBER, MR
中科院分区：
文献类型：
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作者：
GAUSS, GH;LIEBER, MR
基因组中识别位点之间的V(D)J重组具有一定的偏倚性。在某些位点，近端位点比远端位点更频繁地进行重组。D(H)/J(H)的结合就是一个例子。由于D(H)元件每侧都有信号序列，因此在D(H)/J(H)重组中，反转和缺失的频率一样高。然而，明显有利的结果是删除，需要利用更接近的重组位点。一种用来解释这些偏差的模型是重组酶从一个位点追踪到另一个位点的追踪模型。在这里，我们直接测试了V(D)J重组中各种类型的跟踪，并没有发现它发生的迹象。此外，我们还创建了D(H)-J(H)微聚焦底物，以分析其选择性缺失的基础。我们发现我们可以重现系统的删除偏差。此外，通过翻转D段的方向，我们可以反转偏置，这样反转的频率可以超过删除的次数。这些结果表明：(1)该反应不存在固有的拓扑偏好，(2)信号端和编码端的顺序决定了偏置。
V(D)J recombination between recognition sites in the genome is characterized by certain biases. At some loci, proximal sites undergo recombination substantially more frequently than distal ones. The joining of D(H)/J(H) is an example of this. Because the D(H) element bears signal sequences on each side, inversion would be expected as often as deletion in D(H)/J(H) recombination. However, the markedly favored outcome is deletion, entailing utilization of the closer recombination site. One model proposed to explain these biases is the tracking model in which the recombinase tracks from one site to the other. Here, we have directly tested for various types of tracking in V(D)J recombination and have found no indication that it occurs. In addition, we have created D(H)-J(H) minilocus substrates for analysis of the basis for the preference for deletion. We find that we can reproduce the deletional bias for the system. Moreover, by flipping the orientation of the D segment, we can reverse the bias such that the frequency of inversions can exceed the number of deletions. These results indicate (1) that there is no intrinsic topological preference in this reaction, and (2) that the sequence of the signal and coding ends determines the bias.