Probing the telomere damage response.
Probing the telomere damage response.
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DOI：
10.1007/978-1-61779-092-8_14
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Chang, Sandy
中科院分区：
文献类型：
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作者：
Rai, Rekha;Chang, Sandy
端粒功能障碍是由于端粒DNA的复制磨损或由于庇护蛋白成分的抑制而产生的，被认为是DNA损伤修复（DDR）途径中的DNA双链断裂（DSBs）。这导致DNA损伤检查点传感器的激活，包括Mre11-Rad50-Nbs1 （MRN）复合物、γ-H2AX和53BP1、ATM和ATR信号转导激酶以及下游效应物，包括Chk1、Chk2和p53。通过TRF2的完全缺失或显性负突变TPP1ΔRD的表达，功能失调端粒上的DNA损伤应答信号可以通过与γ-H2AX和53BP1形成“端粒功能障碍诱导灶（TIFs）”的关联来检测。端粒诱导TIFs提供了一个量化端粒功能障碍程度和监测信号通路的机会。
Telomere dysfunctions, rendered through replicative attrition of telomeric DNA or due to the inhibition of shelterin components, are recognized as DNA double stranded breaks (DSBs) by the DNA damage repair (DDR) pathway. This leads to the activation of DNA damage checkpoint sensors including the Mre11-Rad50-Nbs1 (MRN) complex, γ-H2AX and 53BP1, the ATM and ATR signal transducing kinases and downstream effectors including Chk1, Chk2 and p53. Robust DNA damage response signals at dysfunctional telomeres, achieved by complete deletion of TRF2 or by expressing dominant negative mutant TPP1ΔRD, can be detected by their association with γ-H2AX and 53BP1 forming “telomere dysfunction induced foci (TIFs)”. Induction of TIFs at telomeres provides an opportunity to quantify the extent of telomere dysfunction and monitor the signaling pathways.