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Mutagenicity Profile Induced by UVB Light in Human Xeroderma Pigmentosum Group C Cells†
Photochemistry and Photobiology ( IF 2.6 ) Pub Date : 2021-09-13 , DOI: 10.1111/php.13516
Nathalia Quintero-Ruiz 1 , Camila Corradi 1 , Natália Cestari Moreno 1, 2 , Tiago Antonio de Souza 1, 3 , Ligia Pereira Castro 1 , Clarissa Ribeiro Reily Rocha 1, 4 , Carlos Frederico Martins Menck 1
Affiliation  

Nucleotide excision repair (NER) is one of the main pathways for genome protection against structural DNA damage caused by sunlight, which in turn is extensively related to skin cancer development. The mutation spectra induced by UVB were investigated by whole-exome sequencing of randomly selected clones of NER-proficient and XP-C-deficient human skin fibroblasts. As a model, a cell line unable to recognize and remove lesions (XP-C) was used and compared to the complemented isogenic control (COMP). As expected, a significant increase of mutagenesis was observed in irradiated XP-C cells, mainly C>T transitions, but also CC>TT and C>A base substitutions. Remarkably, the C>T mutations occur mainly at the second base of dipyrimidine sites in pyrimidine-rich sequence contexts, with 5′TC sequence the most mutated. Although T>N mutations were also significantly increased, they were not directly related to pyrimidine dimers. Moreover, the large-scale study of a single UVB irradiation on XP-C cells allowed recovering the typical mutation spectrum found in human skin cancer tumors. Eventually, the data may be used for comparison with the mutational profiles of skin tumors obtained from XP-C patients and may help to understand the mutational process in nonaffected individuals.

中文翻译:

UVB 光在人类色素性干皮病 C 组细胞中诱导的致突变性特征†

核苷酸切除修复 (NER) 是基因组保护免受阳光引起的结构 DNA 损伤的主要途径之一,而阳光引起的结构 DNA 损伤又与皮肤癌的发展密切相关。通过对随机选择的 NER 熟练和 XP-C 缺陷人类皮肤成纤维细胞的克隆进行全外显子组测序,研究了 UVB 诱导的突变谱。作为模型,使用了不能识别和去除病变的细胞系 (XP-C),并与补充的同基因对照 (COMP) 进行了比较。正如预期的那样,在受照射的 XP-C 细胞中观察到诱变显着增加,主要是 C>T 转换,还有 CC>TT 和 C>A 碱基取代。值得注意的是,C>T 突变主要发生在富含嘧啶的序列环境中二嘧啶位点的第二个碱基处,其中 5'T C 序列突变最多。尽管 T>N 突变也显着增加,但它们与嘧啶二聚体没有直接关系。此外,对 XP-C 细胞进行单次 UVB 照射的大规模研究允许恢复在人类皮肤癌肿瘤中发现的典型突变谱。最终,这些数据可用于与从 XP-C 患者获得的皮肤肿瘤的突变谱进行比较,并可能有助于了解未受影响个体的突变过程。
更新日期:2021-09-13
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