Caf1 regulates translocation of ribonucleotide reductase by releasing nucleoplasmic Spd1-Suc22 assembly.
Caf1 regulates translocation of ribonucleotide reductase by releasing nucleoplasmic Spd1-Suc22 assembly.
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DOI：
10.1093/nar/gkm015
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发表时间：
2007
影响因子：
14.9
通讯作者：
Katada, Toshiaki
中科院分区：
文献类型：
--
作者：
Takahashi, Shinya;Kontani, Kenji;Araki, Yasuhiro;Katada, Toshiaki
核糖核苷酸还原酶(RNR)复合体提供适当的脱氧核糖核苷酸是DNA复制和修复所必需的。最近在裂殖酵母中RNR激活的一个新模型是调节亚单位Suc22从核质到细胞质的移位。RNR抑制蛋白Spd1将Suc22保留在核质中，在DNA复制胁迫下迅速降解，导致Suc22释放，在细胞质中形成活性RNR复合体。在这里，我们证明了CAF1是CCR4-NOT复合体的一个组成部分，负责抵抗复制压力和控制Suc22易位。CAF1不仅是胁迫诱导的Suc22从核质到细胞质转位所必需的，也是核质Spd1降解所必需的。DNA复制压力似乎允许CAF1与Suc22相互作用，导致核质Spd1-Suc22组装的释放。综上所述，这些结果表明CAF1在应激诱导的RNR激活过程中具有一种新的关键调节功能。
Appropriate supply of deoxyribonucleotides by the ribonucleotide reductase (RNR) complex is essential for DNA replication and repair. One recent model for the RNR activation in Schizosaccharomyces pombe is translocation of the regulatory subunit Suc22 from the nucleoplasm to the cytoplasm. The RNR inhibitory protein Spd1, which retains Suc22 in the nucleoplasm, is rapidly degraded upon DNA-replication stress, resulting in release of Suc22 to form the active RNR complex in the cytoplasm. Here, we show that Caf1, a component of the Ccr4–Not complex, is responsible for resistance of the replication stress and control of the Suc22 translocation. Caf1 is required not only for the stress-induced translocation of Suc22 from nucleoplasm to cytoplasm but also for the degradation of nucleoplasmic Spd1. DNA-replication stress appears to allow Caf1 to interact with Suc22, resulting in release of the nucleoplasmic Spd1–Suc22 assembly. Taken together, these results suggest a novel function of Caf1 as a key regulator in the stress-induced RNR activation.