Characteristics of sequences around individual nucleotide substitutions in IgVH genes suggest different GC and AT mutators.
Characteristics of sequences around individual nucleotide substitutions in IgVH genes suggest different GC and AT mutators.
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IgVH 基因中各个核苷酸取代周围的序列特征表明存在不同的 GC 和 AT 突变子。
DOI：
10.4049/jimmunol.162.11.6596
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发表时间：
1999
影响因子：
4.4
通讯作者：
D. Dunn
中科院分区：
文献类型：
--
作者：
J. Spencer;M. Dunn;D. Dunn
体细胞超突变在T依赖性B细胞应答期间影响IG基因，并且特征在于高频率的单碱基置换。超突变并不是一个完全随机的过程;对不同系统中突变的研究揭示了靶向突变的序列基序的存在。在最近对框外人IgVH基因中单个突变碱基周围的序列的分析中，我们发现突变的G和C周围的靶基序是彼此的反向互补。这一发现表明超突变作用于DNA的两条链，这与A和T突变中观察到的偏倚以及转录机制的参与所表明的链依赖性机制的证据相矛盾。我们现在已经扩展了我们的框外基因数据库，并确定了突变的A和T核苷酸侧翼的序列基序。此外，我们已经分别分析了不同类型的核苷酸取代的侧翼序列。我们的研究结果证实了G和C突变的基序之间的关系，并表明突变的A和T的周围的基序是较弱的，并没有相同的关系。结合我们在框外基因中观察到的A/T链偏好，这一观察结果表明，存在一种链不依赖性的双靶G/C突变子和一种链依赖性的单独A/T突变子，并且对局部靶序列的依赖性较低。
Somatic hypermutation affects Ig genes during T-dependent B cell responses and is characterized by a high frequency of single base substitutions. Hypermutation is not a completely random process; a study of mutations in different systems has revealed the presence of sequence motifs that target mutation. In a recent analysis of the sequences surrounding individual mutated bases in out-of-frame human IgVH genes, we found that the target motifs around mutated G's and C's are reverse complements of each other. This finding suggests that hypermutation acts on both strands of DNA, which contradicts evidence of a strand-dependent mechanism as suggested by an observed bias in A and T mutations and the involvement of transcriptional machinery. We have now extended our database of out-of-frame genes and determined the sequence motifs flanking mutated A and T nucleotides. In addition, we have analyzed the flanking sequences for different types of nucleotide substitutions separately. Our results confirm the relationship between the motifs for G and C mutations and show that the motifs surrounding mutated A's and T's are weaker and do not have the same relationship. Taken together with our observation of A/T strand bias in out-of-frame genes, this observation suggests that there is a semitargeted G/C mutator that is strand-independent and a separate A/T mutator that is strand-dependent and is less reliant on the local target sequence.
使用单细胞聚合酶链反应分析人外周 B 细胞的重链库。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Brezinschek,HP;Brezinschek,RI;Lipsky,PE
通讯作者：
Lipsky,PE
分析非生产性重排的人类可变重链基因中体细胞突变的频率和模式。
DOI：
--
发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Dorner,T;Brezinschek,HP;Brezinschek,RI;Foster,SJ;Domiati-Saad,R;Lipsky,PE
通讯作者：
Lipsky,PE