Proietti De Santis Luca, Balajee Adayabalam S, Lorenti Garcia Claudia, Pepe Gaetano, Worboys Ana Montes, Palitti Fabrizio
Laboratorio di Citogenetica Molecolare e Mutagenesi, DABAC, Università degli Studi della Tuscia, 01100 Viterbo, Italy.
DNA Repair (Amst). 2003 Aug 12;2(8):891-900. doi: 10.1016/s1568-7864(03)00088-0.
Cockayne syndrome (CS) is a human autosomal recessive disorder characterized by many neurological and developmental abnormalities. CS cells are defective in transcription coupled repair (TCR) pathway that removes DNA damage from the transcribed strand of active genes. In spite of a TCR deficiency at the cellular level, CS patients do not develop cancer. The lack of cancer incidence in CS patients may be due to the selective elimination of cells by an apoptotic pathway. In order to verify the role of p53-associated pathway in ultraviolet (UV) induced apoptosis in human CS-B cells, the expression of p53 and p53 responsive genes was analysed in UV irradiated human cells after treatment with pifithrin-alpha (PFTalpha). PTFalpha effectively inhibited the induction of p53, p21 and Bax after UV treatment without affecting the apoptotic response in CS-B cells. Our results indicate that the p53-associated pathway involving p21 and Bax does not largely contribute to UV induced apoptosis in TCR defective human CS-B cells.
科凯恩综合征（CS）是一种常染色体隐性遗传病，其特征为多种神经和发育异常。CS细胞在转录偶联修复（TCR）途径存在缺陷，该途径负责从活跃基因的转录链上去除DNA损伤。尽管在细胞水平上存在TCR缺陷，但CS患者不会患癌症。CS患者癌症发病率低可能是由于凋亡途径对细胞的选择性清除。为了验证p53相关途径在紫外线（UV）诱导的人CS - B细胞凋亡中的作用，在用pifithrin - alpha（PFTalpha）处理后，分析了紫外线照射的人细胞中p53及其反应基因的表达。PFTalpha有效抑制了紫外线处理后p53、p21和Bax的诱导，而不影响CS - B细胞的凋亡反应。我们的结果表明，涉及p21和Bax的p53相关途径在TCR缺陷的人CS - B细胞中对紫外线诱导的凋亡作用不大。
