STAT3 modulates the DNA damage response pathway
STAT3 modulates the DNA damage response pathway
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DOI：
10.1111/j.1365-2613.2010.00734.x
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发表时间：
2010-12-01
影响因子：
3
通讯作者：
Stephanou, Anastasis
中科院分区：
文献类型：
--
作者：
Barry, Sean P.;Townsend, Paul A.;Stephanou, Anastasis
众所周知，STAT 3转录因子作为抗凋亡因子发挥作用，特别是在许多恶性肿瘤中。最近，我们发现STAT 3具有细胞保护作用，缺乏STAT 3的细胞对氧化应激更敏感。氧化应激的一个关键特征涉及DNA损伤途径的激活。然而，STAT 3的作用或其在响应DNA损伤中的贡献尚未被描述。在目前的研究中，我们发现缺乏STAT 3的细胞在修复受损DNA方面效率较低。此外，STAT 3缺陷细胞显示ATM-Chk 2和ATR-Chk 1途径的活性降低，这两种途径都是感知DNA损伤的重要途径。最后，我们表明，MDC 1，ATM-Chk 2通路的调节器和DNA损伤反应的促进剂，在转录水平上由STAT 3调节。这些发现表明，STAT 3是有效修复受损DNA所必需的，部分通过调节ATM-Chk 2和ATR-Chk 1途径。
P>The STAT3 transcription factor is well known to function as an anti-apoptotic factor, especially in numerous malignancies. Recently we showed that STAT3 is cytoprotective and that cells lacking STAT3 are more sensitive to oxidative stress. A key feature of oxidative stress involves activation of the DNA damage pathway. However, a role for STAT3 or its contribution in response to DNA damage has not been described. In the present study we show that cells lacking STAT3 are less efficient in repairing damaged DNA. Moreover, STAT3 deficient cells show reduced activity of the ATM-Chk2 and ATR-Chk1 pathways, both important pathways in sensing DNA damage. Finally we show that MDC1, a regulator of the ATM-Chk2 pathway and facilitator of the DNA damage response, is modulated by STAT3 at the transcriptional level. These findings demonstrate that STAT3 is necessary for efficient repair of damaged DNA, partly by modulating the ATM-Chk2 and ATR-Chk1 pathways.