B淋巴细胞中AID引发的DNA损伤的产生与修复。
Generation and repair of AID-initiated DNA lesions in B lymphocytes.
作者信息
Chen Zhangguo, Wang Jing H
机构信息
Integrated Department of Immunology, University of Colorado Anschutz Medical Campus and National Jewish Health, Denver, CO, 80206, USA.
出版信息
Front Med. 2014 Jun;8(2):201-16. doi: 10.1007/s11684-014-0324-4. Epub 2014 Apr 21.
Activation-induced deaminase (AID) initiates the secondary antibody diversification process in B lymphocytes. In mammalian B cells, this process includes somatic hypermutation (SHM) and class switch recombination (CSR), both of which require AID. AID induces U:G mismatch lesions in DNA that are subsequently converted into point mutations or DNA double stranded breaks during SHM/CSR. In a physiological context, AID targets immunoglobulin (Ig) loci to mediate SHM/CSR. However, recent studies reveal genome-wide access of AID to numerous non-Ig loci. Thus, AID poses a threat to the genome of B cells if AID-initiated DNA lesions cannot be properly repaired. In this review, we focus on the molecular mechanisms that regulate the specificity of AID targeting and the repair pathways responsible for processing AID-initiated DNA lesions.
活化诱导的胞嘧啶脱氨酶（AID）启动B淋巴细胞中的二次抗体多样化过程。在哺乳动物B细胞中，这个过程包括体细胞高频突变（SHM）和类别转换重组（CSR），这两者都需要AID。AID在DNA中诱导U:G错配损伤，这些损伤随后在SHM/CSR过程中转化为点突变或DNA双链断裂。在生理环境中，AID靶向免疫球蛋白（Ig）基因座以介导SHM/CSR。然而，最近的研究揭示AID在全基因组范围内可作用于众多非Ig基因座。因此，如果AID引发的DNA损伤不能得到妥善修复，AID就会对B细胞的基因组构成威胁。在这篇综述中，我们重点关注调节AID靶向特异性的分子机制以及负责处理AID引发的DNA损伤的修复途径。
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