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首页> 外文期刊>Cell cycle >The dNTP triphosphohydrolase activity of SAMHD1 persists during S-phase when the enzyme is phosphorylated at T592
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The dNTP triphosphohydrolase activity of SAMHD1 persists during S-phase when the enzyme is phosphorylated at T592

机译：当酶在T592磷酸化时，SamHD1的DNTP三磷酸酶活性持续存在

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摘要

SAMHD1 is the major catabolic enzyme regulating the intracellular concentrations of DNA precursors (dNTPs). The S-phase kinase CDK2-cyclinA phosphorylates SAMHD1 at Thr-592. How this modification affects SAMHD1 function is highly debated. We investigated the role of endogenous SAMHD1 phosphorylation during the cell cycle. Thr-592 phosphorylation occurs first at the G1/S border and is removed during mitotic exit parallel with Thr-phosphorylations of most CDK1 targets. Differential sensitivity to the phosphatase inhibitor okadaic acid suggested different involvement of the PP1 and PP2 families dependent upon the time of the cell cycle. SAMHD1 turn-over indicates that Thr-592 phosphorylation does not cause rapid protein degradation. Furthermore, SAMHD1 influenced the size of the four dNTP pools independently of its phosphorylation. Our findings reveal that SAMHD1 is active during the entire cell cycle and performs an important regulatory role during S-phase by contributing with ribonucleotide reductase to maintain dNTP pool balance for proper DNA replication.
机译：Samhd1是调节DNA前体（DNTPS）细胞内浓度的主要分解酵母酶。 S相激酶CDK2-水苯酮磷酸化SAMHD1在THR-592。这种修改如何影响Samhd1功能是高度辩论的。我们研究了内源性Samhd1磷酸化在细胞周期中的作用。 Thr-592磷酸化首先发生在G1 / s边界处，并且在有丝分裂出口期间与大多数CDK1靶的Thr-磷酸化平行。磷酸酶抑制剂的差异敏感性Okadaic酸提出了PP1和PP2系列依赖于细胞周期的时间的不同累伤。 Samhd1转弯表明Thr-592磷酸化不会导致快速蛋白质降解。此外，Samhd1独立于其磷酸化影响了四个DNTP池的大小。我们的研究结果表明，SamHD1在整个细胞周期中活跃，通过促进核糖核苷酸还原酶来对S阶段进行重要的调节作用，以维持DNTP池平衡以进行适当的DNA复制。

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