AID and somatic hypermutation.
AID and somatic hypermutation.
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DOI：
10.1016/s0065-2776(10)05006-6
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发表时间：
2010
影响因子：
--
通讯作者：
Gearhart, Patricia J.
中科院分区：
文献类型：
--
作者：
Maul, Robert W.;Gearhart, Patricia J.
在受到外来生物体攻击时，外周B细胞可通过对其基因组DNA进行体细胞突变来改变其抗体亲和力和同种型。鉴于基因改变可能导致人类疾病和癌症的潜在后果，细胞改变其DNA的能力是特殊的。因此，正如所预期的那样，这种抗体多样性机制通过一种蛋白质——激活诱导胞苷脱氨酶（AID）受到严格的调控和协调。AID通过在免疫球蛋白基因座内将胞嘧啶转化为尿嘧啶来产生多样性。当脱氧尿嘧啶残基与脱氧鸟苷配对时具有致突变性，因为它在DNA复制过程中模拟胸苷。此外，B细胞可以操纵DNA修复途径，使得脱氧尿嘧啶不能被准确修复。因此，存在一种复杂的平衡，在多个阶段受到调控，以促进免疫球蛋白基因的突变，同时保持基因组其余部分的完整性。在此，我们讨论并总结目前对AID如何引发体细胞高频突变的理解。
In response to an assault by foreign organisms, peripheral B cells can change their antibody affinity and isotype by somatically mutating their genomic DNA. The ability of a cell to modify its DNA is exceptional in light of the potential consequences of genetic alterations to cause human disease and cancer. Thus, as expected, this mechanism of antibody diversity is tightly regulated and coordinated through one protein, activation induced deaminase (AID). AID produces diversity by converting cytosine to uracil within the immunoglobulin loci. The deoxyuracil residue is mutagenic when paired with deoxyguanosine, since it mimics thymidine during DNA replication. Additionally, B cells can manipulate the DNA repair pathways so that deoxyuracils are not faithfully repaired. Therefore, an intricate balance exists which is regulated at multiple stages to promote mutation of immunoglobulin genes, while retaining integrity of the rest of the genome. Here we discuss and summarize the current understanding of how AID functions to cause somatic hypermutation.