Triplex-Induced DNA Damage Response
Triplex-Induced DNA Damage Response
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发表时间：
2013-12
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通讯作者：
F. Rogers;M. Tiwari
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作者：
F. Rogers;M. Tiwari
细胞DNA损伤反应对于在暴露于遗传毒性应激后保持基因组完整性至关重要。一系列复杂的网络和信号通路在DNA损伤后被激活，并触发适当的细胞反应，包括细胞周期停滞，DNA修复和凋亡。所引起的反应取决于持续损伤的类型和程度，最终目标是防止受损DNA的繁殖。我们的研究的一个主要重点是确定参与加工损伤的改变螺旋结构，特别是三链体的细胞途径。我们的实验室已经证明，TFIIH因子XPD在响应三链诱导的DNA链断裂而触发细胞凋亡方面发挥着核心作用。我们已经证明XPD与γH2AX共定位，并且它的存在是H2AX酪氨酸142磷酸化所必需的，其刺激信号通路以将促凋亡因子募集到损伤部位。在此，我们研究了响应于三链体形成而激活的细胞通路，并讨论了我们的发现，该发现表明XPD依赖性细胞凋亡在存在过度结构诱导的DNA损伤的情况下在保护基因组完整性方面起作用。
Cellular DNA damage response is critical to preserving genomic integrity following exposure to genotoxic stress. A complex series of networks and signaling pathways become activated after DNA damage and trigger the appropriate cellular response, including cell cycle arrest, DNA repair, and apoptosis. The response elicited is dependent upon the type and extent of damage sustained, with the ultimate goal of preventing propagation of the damaged DNA. A major focus of our studies is to determine the cellular pathways involved in processing damage induced by altered helical structures, specifically triplexes. Our lab has demonstrated that the TFIIH factor XPD occupies a central role in triggering apoptosis in response to triplex-induced DNA strand breaks. We have shown that XPD co-localizes with γH2AX, and its presence is required for the phosphorylation of H2AX tyrosine142, which stimulates the signaling pathway to recruit pro-apoptotic factors to the damage site. Herein, we examine the cellular pathways activated in response to triplex formation and discuss our finding that suggests that XPD-dependent apoptosis plays a role in preserving genomic integrity in the presence of excessive structurally induced DNA damage.