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Mec1 Is Activated at the Onset of Normal S Phase by Low-dNTP Pools Impeding DNA Replication.
Molecular Cell ( IF 14.5 ) Pub Date : 2020-03-12 , DOI: 10.1016/j.molcel.2020.02.021 Romain Forey 1 , Ana Poveda 2 , Sushma Sharma 3 , Antoine Barthe 1 , Ismael Padioleau 1 , Claire Renard 1 , Robin Lambert 1 , Magdalena Skrzypczak 4 , Krzysztof Ginalski 4 , Armelle Lengronne 1 , Andrei Chabes 3 , Benjamin Pardo 1 , Philippe Pasero 1
Molecular Cell ( IF 14.5 ) Pub Date : 2020-03-12 , DOI: 10.1016/j.molcel.2020.02.021 Romain Forey 1 , Ana Poveda 2 , Sushma Sharma 3 , Antoine Barthe 1 , Ismael Padioleau 1 , Claire Renard 1 , Robin Lambert 1 , Magdalena Skrzypczak 4 , Krzysztof Ginalski 4 , Armelle Lengronne 1 , Andrei Chabes 3 , Benjamin Pardo 1 , Philippe Pasero 1
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The Mec1 and Rad53 kinases play a central role during acute replication stress in budding yeast. They are also essential for viability in normal growth conditions, but the signal that activates the Mec1-Rad53 pathway in the absence of exogenous insults is currently unknown. Here, we show that this pathway is active at the onset of normal S phase because deoxyribonucleotide triphosphate (dNTP) levels present in G1 phase may not be sufficient to support processive DNA synthesis and impede DNA replication. This activation can be suppressed experimentally by increasing dNTP levels in G1 phase. Moreover, we show that unchallenged cells entering S phase in the absence of Rad53 undergo irreversible fork collapse and mitotic catastrophe. Together, these data indicate that cells use suboptimal dNTP pools to detect the onset of DNA replication and activate the Mec1-Rad53 pathway, which in turn maintains functional forks and triggers dNTP synthesis, allowing the completion of DNA replication.
中文翻译：
通过阻止DNA复制的低dNTP池在正常S期开始时激活Mec1。
Mec1和Rad53激酶在发芽酵母中的急性复制应激过程中起着核心作用。它们对于正常生长条件下的生存力也是必不可少的，但是目前尚不清楚在没有外源性侮辱的情况下激活Mec1-Rad53途径的信号。在这里，我们显示此途径在正常S期开始时是有活性的，因为G1期中存在的三磷酸脱氧核糖核苷酸（dNTP）可能不足以支持进行性DNA合成并阻碍DNA复制。可以通过增加G1期的dNTP水平来抑制这种激活。此外，我们表明，在没有Rad53的情况下进入S期的未受挑战的细胞会经历不可逆的前叉塌陷和有丝分裂灾难。一起，
更新日期：2020-03-12
中文翻译：
通过阻止DNA复制的低dNTP池在正常S期开始时激活Mec1。
Mec1和Rad53激酶在发芽酵母中的急性复制应激过程中起着核心作用。它们对于正常生长条件下的生存力也是必不可少的，但是目前尚不清楚在没有外源性侮辱的情况下激活Mec1-Rad53途径的信号。在这里，我们显示此途径在正常S期开始时是有活性的，因为G1期中存在的三磷酸脱氧核糖核苷酸（dNTP）可能不足以支持进行性DNA合成并阻碍DNA复制。可以通过增加G1期的dNTP水平来抑制这种激活。此外，我们表明，在没有Rad53的情况下进入S期的未受挑战的细胞会经历不可逆的前叉塌陷和有丝分裂灾难。一起，
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