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染色体外底物上免疫球蛋白类别转换序列重组断点周围的不对称突变。

Asymmetric mutation around the recombination break point of immunoglobulin class switch sequences on extrachromosomal substrates.

作者信息

Li J, Daniels G A, Lieber M R

机构信息

Division of Molecular Oncology, and Center for Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.

出版信息

Nucleic Acids Res. 1996 Jun 1;24(11):2104-11. doi: 10.1093/nar/24.11.2104.

DOI:10.1093/nar/24.11.2104
PMID:8668542
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC145906/
Abstract

Junctions at class switch recombination sites in the genome are characterized by a unique sequence feature. Nucleotide substitutions and small deletions are common on either of the two sides of the switch junction, but not on both together. We have previously reported an extrachromosomal substrate assay system for analyzing the recombination of class switch sequences. Here we have sequenced nine junctions on each side of the break point and compared these to 17 recombination junctions of control substrates from the same cells. Five of the nine switch recombination junctions have nucleotide substitutions and deletions, with multiple nucleotide changes being more common. Furthermore, mutations were found only on a single side of the junction, just as for the recombination of switch sequences in the genome. In contrast, only one of 17 control substrate junctions had a mutation, and this was a single nucleotide insertion. This difference is highly significant (P < 0.00007) and indicates that the fundamental recombination mechanism is likely to be similar for switch sequences in the chromosome and on minichromosome substrates.

摘要

基因组中类别转换重组位点处的连接具有独特的序列特征。核苷酸替换和小片段缺失在转换连接两侧的任一侧都很常见,但不会同时出现在两侧。我们之前报道过一种用于分析类别转换序列重组的染色体外底物检测系统。在此,我们对断点两侧的九个连接进行了测序,并将其与来自同一细胞的对照底物的17个重组连接进行比较。九个转换重组连接中有五个存在核苷酸替换和缺失,多个核苷酸变化更为常见。此外,正如基因组中转换序列的重组情况一样,突变仅出现在连接的一侧。相比之下,17个对照底物连接中只有一个发生了突变,且是单个核苷酸插入。这种差异具有高度显著性(P < 0.00007),表明染色体和微型染色体底物上的转换序列的基本重组机制可能相似。

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本文引用的文献

1
Affinity maturation and class switching.亲和力成熟和类别转换。
Curr Opin Immunol. 1996 Feb;8(1):89-92. doi: 10.1016/s0952-7915(96)80110-5.
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Mutagenesis in mammalian cells induced by triple helix formation and transcription-coupled repair.三链螺旋形成和转录偶联修复诱导的哺乳动物细胞诱变。
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RNA:DNA complex formation upon transcription of immunoglobulin switch regions: implications for the mechanism and regulation of class switch recombination.免疫球蛋白转换区转录时RNA:DNA复合物的形成:对类别转换重组机制及调控的意义
Nucleic Acids Res. 1995 Dec 25;23(24):5006-11. doi: 10.1093/nar/23.24.5006.
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Extent to which homology can constrain coding exon junctional diversity in V(D)J recombination.同源性在V(D)J重组中限制编码外显子连接多样性的程度。
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NF-HB (BSAP) is a repressor of the murine immunoglobulin heavy-chain 3' alpha enhancer at early stages of B-cell differentiation.NF-HB(BSAP)是B细胞分化早期小鼠免疫球蛋白重链3'α增强子的一种阻遏物。
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DNA sequences at immunoglobulin switch region recombination sites.免疫球蛋白转换区重组位点的DNA序列。
Nucleic Acids Res. 1993 Feb 11;21(3):365-72. doi: 10.1093/nar/21.3.365.
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Mechanism and regulation of immunoglobulin isotype switching.免疫球蛋白同种型转换的机制与调控
Adv Immunol. 1993;54:229-70. doi: 10.1016/s0065-2776(08)60536-2.
8
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The transcription factor BSAP (NF-HB) is essential for immunoglobulin germ-line epsilon transcription.转录因子BSAP(NF-κB)对于免疫球蛋白种系ε转录至关重要。
J Immunol. 1994 Mar 15;152(6):2904-11.
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Extrachromosomal eukaryotic DNA substrates for switch recombination: analysis of isotype and cell specificity.用于转换重组的真核细胞外DNA底物:同种型和细胞特异性分析
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