Perturbation of genes is important for somatic hypermutation to increase antibody affinity during B-cell immunity; however, it may also promote carcinogenesis. Previous studies have revealed that transcription is an important process that can induce DNA damage and genomic instability. Transciption-export-2 (TREX-2) complex, which regulates messenger RNA (mRNA) nuclear export, has been studied in the budding yeast Saccharomyces cerevisiae; however, recent studies have started investigating the molecular function of the mammalian TREX-2 complex. The central molecule in the TREX-2 complex, that is, germinal center-associated nuclear protein (GANP), is closely associated with antibody affinity maturation as well as cancer etiology. In this review, we focus on carcinogenesis, lymphomagenesis, and teratomagenesis caused by transcription-coupled DNA damage through GANP and other components of the TREX-2 complex. We review the basic machinery of mRNA nuclear export and transcription-coupled DNA damage. We then briefly describe the immunological relationship between GANP and the affinity maturation of antibodies. Finally, we illustrate that the aberrant expression of the components of the TREX-2 complex, especially GANP, is associated with the etiology of various solid tumors, lymphomas, and testicular teratoma. These components serve as reliable predictors of cancer prognosis and response to chemotherapy.

中文翻译：

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通过 GANP 和 TREX-2 复合物的其他成分进行转录偶联 DNA 损伤引起的癌变

基因扰动对于体细胞超突变非常重要，可增加 B 细胞免疫过程中的抗体亲和力；然而，它也可能促进致癌。先前的研究表明，转录是一个重要的过程，可以诱导 DNA 损伤和基因组不稳定。转录-输出-2 (TREX-2) 复合物可调节信使 RNA (mRNA) 核输出，已在芽殖酵母酿酒酵母中进行了研究；然而，最近的研究已经开始调查哺乳动物 TREX-2 复合物的分子功能。 TREX-2复合物中的中心分子，即生发中心相关核蛋白（GANP），与抗体亲和力成熟以及癌症病因密切相关。在这篇综述中，我们重点关注 GANP 和 TREX-2 复合物的其他成分导致的转录偶联 DNA 损伤引起的癌变、淋巴瘤发生和畸胎瘤发生。我们回顾了 mRNA 核输出和转录偶联 DNA 损伤的基本机制。然后我们简要描述 GANP 与抗体亲和力成熟之间的免疫学关系。最后，我们说明TREX-2复合物成分的异常表达，尤其是GANP，与各种实体瘤、淋巴瘤和睾丸畸胎瘤的病因有关。这些成分可以作为癌症预后和化疗反应的可靠预测因子。