Gamma radiation increases endonuclease-dependent L1 retrotransposition in a cultured cell assay.
Gamma radiation increases endonuclease-dependent L1 retrotransposition in a cultured cell assay.
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DOI：
10.1093/nar/gkj522
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发表时间：
2006
影响因子：
14.9
通讯作者：
Prak ET
中科院分区：
文献类型：
--
作者：
Farkash EA;Kao GD;Horman SR;Prak ET
长散布元件（LINE-1，L1）是人类基因组中最活跃的移动的元件，占其质量的很大一部分。L1在人类基因组中的繁殖需要在整合位点处破坏和修复DNA。正如Barbara McClintock首先假设的那样，遗传毒性应激可能有助于转座因子的移动，相反，元件移动性可能有助于遗传毒性应激。我们测试的能力，遗传毒性剂，以增加L1逆转录转座培养细胞测定。我们观察到，暴露于γ射线的细胞表现出L1反转录水平的增加。L1反转录转座频率与磷酸化H2 AX灶的数量成比例，这是遗传毒性应激的指标。为了探索L1核酸内切酶在这种情况下的作用，产生核酸内切酶缺陷的标记L1构建体，并测试其在辐照细胞中的活性。核酸内切酶缺陷型L1的活性在辐照细胞中非常低，表明辐照细胞中的大多数L1插入仍然使用L1核酸内切酶。与这种解释一致，在辐照细胞中侧翼L1插入的DNA序列具有靶位点重复。这些结果表明，在照射细胞中增加的L1反转录转座是核酸内切酶依赖性的。L1在辐射细胞中的动员可能导致基因组的不稳定性，并可能是接受放射治疗的患者继发突变的驱动力。
Long Interspersed Elements (LINE-1s, L1s) are the most active mobile elements in the human genome and account for a significant fraction of its mass. The propagation of L1 in the human genome requires disruption and repair of DNA at the site of integration. As Barbara McClintock first hypothesized, genotoxic stress may contribute to the mobilization of transposable elements, and conversely, element mobility may contribute to genotoxic stress. We tested the ability of genotoxic agents to increase L1 retrotransposition in a cultured cell assay. We observed that cells exposed to gamma radiation exhibited increased levels of L1 retrotransposition. The L1 retrotransposition frequency was proportional to the number of phosphorylated H2AX foci, an indicator of genotoxic stress. To explore the role of the L1 endonuclease in this context, endonuclease-deficient tagged L1 constructs were produced and tested for their activity in irradiated cells. The activity of the endonuclease-deficient L1 was very low in irradiated cells, suggesting that most L1 insertions in irradiated cells still use the L1 endonuclease. Consistent with this interpretation, DNA sequences that flank L1 insertions in irradiated cells harbored target site duplications. These results suggest that increased L1 retrotransposition in irradiated cells is endonuclease dependent. The mobilization of L1 in irradiated cells potentially contributes to genomic instability and could be a driving force for secondary mutations in patients undergoing radiation therapy.
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DOI：
10.3390/ijerph2005010014
发表时间：
2005-04
影响因子：
--
作者：
Kale SP;Moore L;Deininger PL;Roy-Engel AM
通讯作者：
Roy-Engel AM
DOI：
10.1073/pnas.0831042100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Brouha, B;Schustak, J;Kazazian, HH
通讯作者：
Kazazian, HH
影响因子：
14.9
作者：
Cost, GJ;Golding, A;Boeke, JD
通讯作者：
Boeke, JD
影响因子：
64.5
作者：
Gilbert, N;Lutz-Prigge, S;Moran, JV
通讯作者：
Moran, JV
影响因子：
4
作者：
Kazazian, HH
通讯作者：
Kazazian, HH