Reynaud C A, Frey S, Aoufouchi S, Faili A, Bertocci B, Dahan A, Flatter E, Delbos F, Storck S, Zober C, Weill J C
Institut National de la Santé et de la Recherche Médicale U373, Faculté de Médecine Necker-Enfants Malades, Université Paris V, France.
Philos Trans R Soc Lond B Biol Sci. 2001 Jan 29;356(1405):91-7. doi: 10.1098/rstb.2000.0753.
This paper discusses two aspects of immunoglobulin (Ig) gene hypermutation. In the first approach, a transcription termination signal is introduced in an Ig light chain transgene acting as a mutation substrate, and transgenic lines are generated with control and mutant transgenes integrated in tandem. Analysis of transcription levels and mutation frequencies between mutant and control transgenes clearly dissociates transcription elongation and mutation, and therefore argues against models whereby specific pausing of the RNA polymerase during V gene transcription would trigger an error-prone repair process. The second part reports the identification of two novel beta-like DNA polymerases named Pol lambda and Pol mu, one of which (Pol mu) represents a good candidate for the Ig mutase due to its higher lymphoid expression and its similarity with the lymphoid enzyme terminal deoxynucleotidyl transferase. Peculiar features of the expression of this gene, including an unusual splicing variability and a splicing inhibition in response to DNA-damaging agents, are discussed.
本文讨论了免疫球蛋白（Ig）基因超突变的两个方面。在第一种方法中，在作为突变底物的Ig轻链转基因中引入转录终止信号，并生成串联整合有对照和突变转基因的转基因系。对突变和对照转基因之间的转录水平和突变频率进行分析，清楚地将转录延伸与突变区分开来，因此反对那种认为V基因转录过程中RNA聚合酶的特定停顿会触发易错修复过程的模型。第二部分报告了两种新型β样DNA聚合酶（命名为Pol λ和Pol μ）的鉴定，其中一种（Pol μ）由于其在淋巴组织中的高表达以及与淋巴组织酶末端脱氧核苷酸转移酶的相似性，是Ig突变酶的一个很好的候选者。本文还讨论了该基因表达的独特特征，包括异常的剪接变异性以及对DNA损伤剂的剪接抑制。
