Sodium tungstate modulates ATM function upon DNA damage

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• 作者：C.J. Rodriguez-Hern ; ez ; M. Llorens-Agost ; J. Calb¨® ; J.R. Murguia ; J.J. Guinovart
• 关键词：DNA damage ; Antitumoral ; Double-strand break ; Phosphatase inhibition
• 刊名：FEBS Letters
• 出版年：2013
• 出版时间：21 May, 2013
• 年：2013
• 卷：587
• 期：10
• 页码：1579-1586
• 全文大小：1241 K

文摘

Both radiotherapy and most effective chemotherapeutic agents induce different types of DNA damage. Here we show that tungstate modulates cell response to DNA damaging agents. Cells treated with tungstate were more sensitive to etoposide, phleomycin and ionizing radiation (IR), all of which induce DNA double-strand breaks (DSBs). Tungstate also modulated the activation of the central DSB signalling kinase, ATM, in response to these agents. These effects required the functionality of the Mre11-Nbs1-Rad50 (MRN) complex and were mimicked by the inhibition of PP2A phosphatase. Therefore, tungstate may have adjuvant activity when combined with DNA-damaging agents in the treatment of several malignancies.