首页>
外文期刊>The journal of immunology
>Cutting Edge: DGYW/WRCH Is a Better Predictor of Mutability at G:C Bases in Ig Hypermutation Than the Widely Accepted RGYW/WRCY Motif and Probably Reflects a Two-Step Activation-Induced Cytidine Deaminase-Triggered Process
【24h】
Cutting Edge: DGYW/WRCH Is a Better Predictor of Mutability at G:C Bases in Ig Hypermutation Than the Widely Accepted RGYW/WRCY Motif and Probably Reflects a Two-Step Activation-Induced Cytidine Deaminase-Triggered Process
A feature of Ig hypermutation is the presence of hypermutable DNA sequences that are preferentially found in the V regions of Ig genes. Among these, RGYW/WRCY is the most pronounced motif (G:C is a mutable position; R = A/G, Y = C/T, and W = A/T). However, a molecular basis for the high mutability of RGYW was not known until recently. The discovery that activation-induced cytidine deaminase targets the DNA encoding V regions, has enabled the analysis of its targeting properties when expressed outside of the context of hypermutation. We analyzed these data and found evidence that activation-induced cytidine deaminase is the major source of the RGYW mutable motif, but with a new twist: DGYW/WRCH (G:C is the mutable position; D = A/G/T, H = T/C/A) is a better descriptor of the Ig mutation hotspot than RGYW/WRCY. We also found evidence that a DNA repair enzyme may play a role in modifying the sequence of hypermutation hotspots.
展开▼
机译:Ig超变的特征是存在优先在Ig基因的V区中发现的超变DNA序列。其中,RGYW / WRCY是最明显的基序(G:C是可变位置; R = A / G,Y = C / T,W = A / T)。但是,直到最近,RGYW的高变异性的分子基础还是未知的。激活诱导的胞苷脱氨酶靶向编码V区的DNA的发现,使得在超突变环境外表达时能够分析其靶向特性。我们分析了这些数据,发现证据表明激活诱导的胞苷脱氨酶是RGYW可变基序的主要来源,但有新的变化:DGYW / WRCH(G:C是可变位置; D = A / G / T,H = T / C / A)比RGYW / WRCY更能说明Ig突变热点。我们还发现有证据表明DNA修复酶可能在修饰超突变热点的序列中起作用。
展开▼