V(D)J重组信号序列切割的DNA序列及结构要求。
DNA sequence and structure requirements for cleavage of V(D)J recombination signal sequences.
作者信息
Cuomo C A, Mundy C L, Oettinger M A
机构信息
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
出版信息
Mol Cell Biol. 1996 Oct;16(10):5683-90. doi: 10.1128/MCB.16.10.5683.
Abstract
Purified RAG1 and RAG2 proteins can cleave DNA at V(D)J recombination signals. In dissecting the DNA sequence and structural requirements for cleavage, we find that the heptamer and nonamer motifs of the recombination signal sequence can independently direct both steps of the cleavage reaction. Proper helical spacing between these two elements greatly enhances the efficiency of cleavage, whereas improper spacing can lead to interference between the two elements. The signal sequences are surprisingly tolerant of structural variation and function efficiently when nicks, gaps, and mismatched bases are introduced or even when the signal sequence is completely single stranded. Sequence alterations that facilitate unpairing of the bases at the signal/coding border activate the cleavage reaction, suggesting that DNA distortion is critical for V(D)J recombination.
摘要
纯化的RAG1和RAG2蛋白可在V(D)J重组信号处切割DNA。在剖析切割所需的DNA序列和结构要求时，我们发现重组信号序列的七聚体和非聚体基序可独立指导切割反应的两个步骤。这两个元件之间适当的螺旋间距可大大提高切割效率，而不适当的间距会导致两个元件之间的干扰。令人惊讶的是，当引入切口、缺口和错配碱基，甚至当信号序列完全为单链时，信号序列对结构变异具有耐受性且能高效发挥功能。促进信号/编码边界处碱基解配对的序列改变会激活切割反应，这表明DNA扭曲对V(D)J重组至关重要。
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本文引用的文献
1
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EMBO J. 1996 Jun 17;15(12):3197-206.
2
Regions of RAG1 protein critical for V(D)J recombination.RAG1蛋白中对V(D)J重组至关重要的区域。
Eur J Immunol. 1996 Apr;26(4):886-91. doi: 10.1002/eji.1830260425.
3
The RAG1 and RAG2 proteins establish the 12/23 rule in V(D)J recombination.RAG1和RAG2蛋白在V(D)J重组中确立了12/23规则。
Cell. 1996 Apr 5;85(1):107-13. doi: 10.1016/s0092-8674(00)81086-7.
4
Similarities between initiation of V(D)J recombination and retroviral integration.V(D)J 重组起始与逆转录病毒整合之间的相似性。
Science. 1996 Mar 15;271(5255):1592-4. doi: 10.1126/science.271.5255.1592.
5
Initiation of V(D)J recombination in vitro obeying the 12/23 rule.体外V(D)J重组的起始遵循12/23规则。
Nature. 1996 Mar 7;380(6569):85-8. doi: 10.1038/380085a0.
6
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Cell. 1995 Nov 3;83(3):387-95. doi: 10.1016/0092-8674(95)90116-7.
7
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8
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9
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10
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Adv Immunol. 1994;56:27-150. doi: 10.1016/s0065-2776(08)60450-2.
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