DNA polymerase η is involved in hypermutation occurring during immunoglobulin class switch recombination
DNA polymerase η is involved in hypermutation occurring during immunoglobulin class switch recombination
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DOI：
10.1084/jem.20031831
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发表时间：
2004-01-19
影响因子：
15.3
通讯作者：
Weill, JC
中科院分区：
文献类型：
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作者：
Faili, A;Aoufouchi, S;Weill, JC
在参与类别转换重组（CSR）的DNA序列的免疫球蛋白基因座上观察到碱基替换、缺失和重复。这些突变依赖于激活诱导的胞苷脱氨酶（AID），并且呈现出在V基因体细胞超突变过程中观察到的所有特征，这意味着它们可能由相同的突变复合物产生。基于易患癌症的着色性干皮病变异型（XP - V）综合征患者（其缺乏DNA聚合酶η（pol η））的V基因突变模式，有人提出这种酶可能对A/T碱基上发生的大部分突变负责。在这里，我们通过分析两名XP - V患者的转换记忆B细胞表明，pol η在CSR过程中也是A/T突变体，无论是在串联重复的转换区域还是其上游，因此表明在这两个过程中，相同的易错跨损伤聚合酶与AID一起参与其中。
Base substitutions, deletions, and duplications are observed at the immunoglobulin locus in DNA sequences involved in class switch recombination (CSR). These mutations are dependent upon activation-induced cytidine deaminase (AID) and present all the characteristics of the ones observed during V gene somatic hypermutation, implying that they could be generated by the same mutational complex. It has been proposed, based on the V gene mutation pattern of patients with the cancer-prone xeroderma pigmentosum variant (XP-V) syndrome who are deficient in DNA polymerase eta (pol eta), that this enzyme could be responsible for a large part of the mutations occurring on A/T bases. Here we show, by analyzing switched memory B cells front two XP-V patients, that pol eta is also an A/T mutator during CSR, in both the switch region of tandem repeats as well as upstream of it, thus suggesting that the same error-prone translesional polymerases are involved, together with AID, in both processes.