Overlapping activation-induced cytidine deaminase hotspot motifs in Ig class-switch recombination
Overlapping activation-induced cytidine deaminase hotspot motifs in Ig class-switch recombination
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DOI：
10.1073/pnas.1018726108
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发表时间：
2011-07-12
影响因子：
11.1
通讯作者：
Yu, Kefei
中科院分区：
文献类型：
--
作者：
Han, Li;Masani, Shahnaz;Yu, Kefei
IG类别转换重组（CSR）由长且重复的转换区域指导，并且需要激活诱导的胞苷脱氨酶（AID）。其中一个保守的开关区序列基序（AGCT）是艾滋病介导的DNA-胞嘧啶脱氨的首选位点。通过使用体细胞基因靶向和重组酶介导的盒交换，我们建立了基于细胞系的CSR测定，其允许在内源基因座处操纵开关序列。我们发现，AGCT是一个家庭的四个WGCW图案的开关区域，可以促进CSR中的一个。我们继续表明，这是在WGCW网站上的顶部和底部链，是至关重要的艾滋病热点的重叠。这一发现为CSR和体细胞超突变之间的差异提供了更清晰的模型。
Ig class-switch recombination (CSR) is directed by the long and repetitive switch regions and requires activation-induced cytidine deaminase (AID). One of the conserved switch-region sequence motifs (AGCT) is a preferred site for AID-mediated DNA-cytosine deamination. By using somatic gene targeting and recombinase-mediated cassette exchange, we established a cell line-based CSR assay that allows manipulation of switch sequences at the endogenous locus. We show that AGCT is only one of a family of four WGCW motifs in the switch region that can facilitate CSR. We go on to show that it is the overlap of AID hotspots at WGCW sites on the top and bottom strands that is critical. This finding leads to a much clearer model for the difference between CSR and somatic hypermutation.