XPD-dependent activation of apoptosis in response to triplex-induced DNA damage.
XPD-dependent activation of apoptosis in response to triplex-induced DNA damage.
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DOI：
10.1093/nar/gkt670
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发表时间：
2013-10
影响因子：
14.9
通讯作者：
Rogers FA
中科院分区：
文献类型：
--
作者：
Kaushik Tiwari M;Rogers FA
能够形成三链体的DNA序列在人类基因组中普遍存在，并且已发现其具有内在致突变性。因此，DNA修复和细胞凋亡之间的平衡对于抵消它们对基因组完整性的影响至关重要。使用三链体形成寡核苷酸合成创建改变的螺旋扭曲，我们已经确定，促凋亡途径被激活的三链体结构的形成。此外，TFIIH因子XPD在响应于三链体诱导的DNA链断裂而触发细胞凋亡中占据中心作用。在这里，我们发现三链体能够诱导XPD非依赖性双链断裂，导致γH2AX灶的形成。XPD随后被募集到三链体诱导的双链断裂，并与γH2AX共定位在损伤部位。此外，发现H2AX酪氨酸142的磷酸化刺激XPD依赖性凋亡的信号通路。我们认为，这种机制可能发挥积极的作用，在尽量减少基因组不稳定性诱导的自然发生的非规范结构，也许防止癌症的启动。
DNA sequences capable of forming triplexes are prevalent in the human genome and have been found to be intrinsically mutagenic. Consequently, a balance between DNA repair and apoptosis is critical to counteract their effect on genomic integrity. Using triplex-forming oligonucleotides to synthetically create altered helical distortions, we have determined that pro-apoptotic pathways are activated by the formation of triplex structures. Moreover, the TFIIH factor, XPD, occupies a central role in triggering apoptosis in response to triplex-induced DNA strand breaks. Here, we show that triplexes are capable of inducing XPD-independent double strand breaks, which result in the formation of γH2AX foci. XPD was subsequently recruited to the triplex-induced double strand breaks and co-localized with γH2AX at the damage site. Furthermore, phosphorylation of H2AX tyrosine 142 was found to stimulate the signaling pathway of XPD-dependent apoptosis. We suggest that this mechanism may play an active role in minimizing genomic instability induced by naturally occurring noncanonical structures, perhaps protecting against cancer initiation.
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影响因子：
64.8
作者：
MIRKIN, SM;LYAMICHEV, VI;FRANKKAMENETSKII, MD
通讯作者：
FRANKKAMENETSKII, MD
DOI：
10.1073/pnas.262556899
发表时间：
2002-12-24
影响因子：
11.1
作者：
Rogers, FA;Vasquez, KM;Glazer, PM
通讯作者：
Glazer, PM
XPD 基因突变会阻止 TFIIH 依赖核受体的转录激活和 RARα 的磷酸化
影响因子：
64.5
作者：
Keriel, A;Stary, A;Egly, JM
通讯作者：
Egly, JM
影响因子：
1.6
作者：
Johnson, MD;Fresco, JR
通讯作者：
Fresco, JR
影响因子：
14.9
作者：
KINNIBURGH, AJ
通讯作者：
KINNIBURGH, AJ