Arabidopsis ATM and ATR Kinases Prevent Propagation of Genome Damage Caused by Telomere Dysfunction
Arabidopsis ATM and ATR Kinases Prevent Propagation of Genome Damage Caused by Telomere Dysfunction
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DOI：
10.1105/tpc.111.092387
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发表时间：
2011-12-01
期刊：
影响因子：
11.6
通讯作者：
Gallego, Maria Eugenia
中科院分区：
文献类型：
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作者：
Amiard, Simon;Depeiges, Annie;Gallego, Maria Eugenia
线性真核染色体的末端隐藏在称为端粒的核蛋白结构中，端粒结构的丢失会导致不适当的修复，导致严重的核型和基因组不稳定。虽然已经证明DNA损伤剂可以激活DNA损伤反应（DDR），但对功能失调的植物端粒的信号传导知之甚少。我们发现，端粒酶的缺失在拟南芥中引发了端粒上的ataxa -毛细血管扩张突变（ATM）和ATM和rad3相关（ATR）依赖的DDR，主要是通过ATM。相比之下，端粒功能障碍在端粒保守端粒维持组分1 (Ctc1)- cdc 13 （Stn1）抑制因子-与Stn1 （CST）复合物突变体相关的端粒通路中诱导atr依赖性反应。这些结果揭示了CST复合物在植物细胞中抑制atr依赖性DDR通路中的新作用，并表明植物细胞使用两种不同的DNA损伤监视通路来指示端粒功能障碍。ctc1和stn1突变体中ATM或ATR的缺失显著增强了发育和基因组的不稳定性，同时减少了干细胞的死亡。因此，这些数据清楚地说明了ATM/ atr依赖性程序性细胞死亡通过消除遗传不稳定的细胞来维持基因组完整性的作用。
The ends of linear eukaryotic chromosomes are hidden in nucleoprotein structures called telomeres, and loss of the telomere structure causes inappropriate repair, leading to severe karyotypic and genomic instability. Although it has been shown that DNA damaging agents activate a DNA damage response (DDR), little is known about the signaling of dysfunctional plant telomeres. We show that absence of telomerase in Arabidopsis thaliana elicits an ATAXIA-TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR)-dependent DDR at telomeres, principally through ATM. By contrast, telomere dysfunction induces an ATR-dependent response in telomeric Conserved telomere maintenance component1 (Ctc1)-Suppressor of cdc thirteen (Stn1)-Telomeric pathways in association with Stn1 (CST)-complex mutants. These results uncover a new role for the CST complex in repressing the ATR-dependent DDR pathway in plant cells and show that plant cells use two different DNA damage surveillance pathways to signal telomere dysfunction. The absence of either ATM or ATR in ctc1 and stn1 mutants significantly enhances developmental and genome instability while reducing stem cell death. These data thus give a clear illustration of the action of ATM/ATR-dependent programmed cell death in maintaining genomic integrity through elimination of genetically unstable cells.