Reynaud Claude-Agnès, Delbos Frédéric, Faili Ahmad, Guéranger Quentin, Aoufouchi Said, Weill Jean-Claude
INSERM U783 Développement du système immunitaire, Université Paris Descartes, Faculté de Médecine, Site Necker-Enfants Malades, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
Philos Trans R Soc Lond B Biol Sci. 2009 Mar 12;364(1517):613-9. doi: 10.1098/rstb.2008.0206.
This review focuses on the contribution of translesion DNA polymerases to immunoglobulin gene hypermutation, in particular on the roles of DNA polymerase eta (Poleta) in the generation of mutations at A/T bases from the initial cytosine-targeted activation-induced cytidine deaminase (AID)-mediated deamination event, and of Polkappa, an enzyme of the same polymerase family, used as a substitute when Poleta is absent. The proposition that the UNG uracil glycosylase and the MSH2-MSH6 mismatch recognition complex are two competitive rather than alternative pathways in the processing of uracils generated by AID is further discussed.
本综述聚焦于跨损伤DNA聚合酶对免疫球蛋白基因超突变的贡献，尤其关注DNA聚合酶η（Polη）在最初由胞嘧啶靶向的激活诱导胞苷脱氨酶（AID）介导的脱氨事件中A/T碱基处突变产生过程中的作用，以及Polκ（同一聚合酶家族的一种酶）在Polη缺失时作为替代酶的作用。文中进一步讨论了UNG尿嘧啶糖基化酶和MSH2-MSH6错配识别复合体在处理由AID产生的尿嘧啶时是两条相互竞争而非替代途径的观点。
