G2/M-checkpoint activation in fasciata1 rescues an aberrant S-phase checkpoint but causes genome instability.
G2/M-checkpoint activation in fasciata1 rescues an aberrant S-phase checkpoint but causes genome instability.
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DOI：
10.1093/plphys/kiab201
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发表时间：
2021-08-03
期刊：
影响因子：
7.4
通讯作者：
De Veylder, Lieven
中科院分区：
文献类型：
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作者：
Eekhout, Thomas;Dvorackova, Martina;De Veylder, Lieven
WEE1 和 ATM 及 RAD3 相关 (ATR) 激酶是植物 S 期内检查点的重要调节因子；因此，WEE1KO 和 ATRKO 根对复制抑制药物高度敏感。在这里，我们报告了染色质组装因子 1 (CAF-1) 复合物的 FASCIATA1 (FAS1) 亚基的功能丧失突变等位基因，该突变等位基因抑制 WEE1 或 ATR 缺陷的拟南芥 (Arabidopsis thaliana) 植物的表型。我们证明，缺乏 FAS1 活性会导致共济失调毛细血管扩张突变 (ATM) 和伽玛响应抑制因子 1 (SOG1) 介导的 G2/M 阻滞的激活，从而使 ATR 和 WEE1 检查点调节因子变得多余。这种 ATM 激活导致了 fas1 植物的端粒侵蚀和核糖体 DNA 丢失。在 fas1 wee1 背景中敲除 SOG1 可恢复复制应激敏感性，表明 SOG1 是无法激活 S 期内检查点的植物中重要的二级检查点调节因子。
The WEE1 and ATM AND RAD3-RELATED (ATR) kinases are important regulators of the plant intra-S-phase checkpoint; consequently, WEE1KO and ATRKO roots are hypersensitive to replication-inhibitory drugs. Here, we report on a loss-of-function mutant allele of the FASCIATA1 (FAS1) subunit of the chromatin assembly factor 1 (CAF-1) complex that suppresses the phenotype of WEE1- or ATR-deficient Arabidopsis (Arabidopsis thaliana) plants. We demonstrate that lack of FAS1 activity results in the activation of an ATAXIA TELANGIECTASIA MUTATED (ATM)- and SUPPRESSOR OF GAMMA-RESPONSE 1 (SOG1)-mediated G2/M-arrest that renders the ATR and WEE1 checkpoint regulators redundant. This ATM activation accounts for the telomere erosion and loss of ribosomal DNA that are described for fas1 plants. Knocking out SOG1 in the fas1 wee1 background restores replication stress sensitivity, demonstrating that SOG1 is an important secondary checkpoint regulator in plants that fail to activate the intra-S-phase checkpoint.