Abnormal regulation of DDB2 gene expression in xeroderma pigmentosum group E strains.
Abnormal regulation of DDB2 gene expression in xeroderma pigmentosum group E strains.
复制标题
着色性干皮病 E 组菌株中 DDB2 基因表达的异常调节。
作者：
Itoh,T;Nichols,A;Linn,S
损伤特异性DNA结合蛋白（DDB）活性不存在于最初被分类为着色性干皮病（XP）E组的个体的细胞亚群（DDB-）中，着色性干皮病是一种遗传性光敏性疾病，具有高的皮肤恶性肿瘤发病率。在这些情况下，已在DDB 2基因（DDB 2 −）中鉴定出突变，该基因编码DDB异源二聚体的小亚基p48。在4个DDB 2 −菌株中，在紫外线照射前后均未观察到p48和DDB活性，尽管紫外线照射后DDB 2 mRNA水平异常强烈地上调。在第五株，XP 82 TO，p48是可检测的，DDB 2 mRNA和p48水平的上调后，紫外线照射比正常的原代细胞。此外，照射后DDB活性也变得明显。与其他DDB−患者相比，XP 82 TO表现出非常轻微的临床表现。这些结果，再加上我们的发现，大多数，如果不是所有的DDB+细胞分类为XP-E被错误分类，表明DDB 2水平和XP-E表型之间的直接相关性。
A damage-specific DNA binding protein (DDB) activity is absent from a subset (DDB−) of cells from individuals initially classified as group E of xeroderma pigmentosum (XP), a hereditary, photosensitive disease with a high incidence of skin malignancies. In these cases, mutations have been identified in the DDB2 gene (DDB2−) that codes for the small subunit, p48, of the DDB heterodimer. In four DDB2− strains, neither p48 nor DDB activity were observed before or after UV-irradiation, despite an unusually strong up-regulation of DDB2 mRNA levels after UV-irradiation. In a fifth strain, XP82TO, p48 was detectable and both DDB2 mRNA and p48 levels were more up-regulated after UV-irradiation than in normal primary cells. Moreover, DDB activity also became apparent after irradiation. XP82TO showed very mild clinical manifestations compared with the other DDB− patients. These results, coupled with our findings that most, if not all DDB+ cells classified as XP-E were misclassified, suggests a direct correlation between DDB2 levels and the XP-E phenotype.