Programmed induction of endoreduplication by DNA double-strand breaks in Arabidopsis
Programmed induction of endoreduplication by DNA double-strand breaks in Arabidopsis
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DOI：
10.1073/pnas.1103584108
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发表时间：
2011-06-14
影响因子：
11.1
通讯作者：
Umeda, Masaaki
中科院分区：
文献类型：
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作者：
Adachi, Sumiko;Minamisawa, Kazunori;Umeda, Masaaki
基因组的完整性不断受到外部压力和内源性危害，如DNA复制错误和活性氧的威胁。后生动物中的DNA损伤检查点通过延迟细胞周期进程以修复受损的DNA或通过诱导细胞凋亡来确保基因组的完整性。ATM和ATR（共济失调毛细血管扩张突变和Rad 3相关）是传感器激酶，将损伤信号传递给转导激酶Chk 1和Chk 2以及下游细胞周期调节因子。植物也具有ATM和ATR的直系同源物，但缺乏明显的下游调控对应物。相反，植物特异性转录因子SOG 1（γ反应抑制因子1）在ATM和ATR激酶的信号传递中起着核心作用。在这里，我们表明，在拟南芥中，核内复制是由DNA双链断裂（DSB），但不是直接由DNA复制胁迫诱导。当根或萼片细胞，或未分化的悬浮细胞，用DSB诱导剂处理，他们表现出增加的细胞大小和DNA倍性。我们发现，ATM-SOG 1和ATR-SOG 1途径都传递DSB衍生的信号，并且任何一个都足以进行内循环诱导。这些信号通路控制不同的细胞周期调节因子的表达，如细胞周期蛋白依赖性激酶及其抑制因子。我们的研究结果表明，拟南芥经历了一个程序化的endoreduplicative响应DSBs，表明植物已经进化出一个独特的策略，以维持在遗传毒性胁迫下的增长。
Genome integrity is continuously threatened by external stresses and endogenous hazards such as DNA replication errors and reactive oxygen species. The DNA damage checkpoint in metazoans ensures genome integrity by delaying cell-cycle progression to repair damaged DNA or by inducing apoptosis. ATM and ATR (ataxia-telangiectasia-mutated and -Rad3-related) are sensor kinases that relay the damage signal to transducer kinases Chk1 and Chk2 and to downstream cell-cycle regulators. Plants also possess ATM and ATR orthologs but lack obvious counterparts of downstream regulators. Instead, the plant-specific transcription factor SOG1 (suppressor of gamma response 1) plays a central role in the transmission of signals from both ATM and ATR kinases. Here we show that in Arabidopsis, endoreduplication is induced by DNA double-strand breaks (DSBs), but not directly by DNA replication stress. When root or sepal cells, or undifferentiated suspension cells, were treated with DSB inducers, they displayed increased cell size and DNA ploidy. We found that the ATM-SOG1 and ATR-SOG1 pathways both transmit DSB-derived signals and that either one suffices for endocycle induction. These signaling pathways govern the expression of distinct sets of cell-cycle regulators, such as cyclin-dependent kinases and their suppressors. Our results demonstrate that Arabidopsis undergoes a programmed endoreduplicative response to DSBs, suggesting that plants have evolved a distinct strategy to sustain growth under genotoxic stress.