Department of Cell Biology, Institute for Cancer Research, Oslo, Norway.
PLoS One. 2012;7(9):e44539. doi: 10.1371/journal.pone.0044539. Epub 2012 Sep 6.
Here we characterize a novel protein in S. pombe. It has a high degree of homology with the Zn-finger domain of the human Poly(ADP-ribose) polymerase (PARP). Surprisingly, the gene for this protein is, in many fungi, fused with and in the same reading frame as that encoding Rad3, the homologue of the human ATR checkpoint protein. We name the protein Hpz1 (Homologue of PARP-type Zn-finger). Hpz1 does not possess PARP activity, but is important for resistance to ultraviolet light in the G1 phase and to treatment with hydroxyurea, a drug that arrests DNA replication forks in the S phase. However, we find no evidence of a checkpoint function of Hpz1. Furthermore, absence of Hpz1 results in an advancement of S-phase entry after a G1 arrest as well as earlier recovery from a hydroxyurea block. The hpz1 gene is expressed mainly in the G1 phase and Hpz1 is localized to the nucleus. We conclude that Hpz1 regulates the initiation of the S phase and may cooperate with Rad3 in this function.
在这里，我们描述了一种新型的 S. pombe 蛋白。它与人多聚（ADP-核糖）聚合酶（PARP）的 Zn 指结构域具有高度同源性。令人惊讶的是，这种蛋白的基因在许多真菌中与编码 Rad3 的基因融合，并在同一阅读框中，Rad3 是人类 ATR 检查点蛋白的同源物。我们将该蛋白命名为 Hpz1（PARP 型 Zn 指同源物）。Hpz1 不具有 PARP 活性，但对 G1 期紫外线照射和羟基脲处理（一种在 S 期阻止 DNA 复制叉的药物）具有重要的抗性。然而，我们没有发现 Hpz1 具有检查点功能的证据。此外，Hpz1 的缺失导致 G1 期阻滞后 S 期进入的提前以及羟基脲阻断后更早的恢复。hpz1 基因主要在 G1 期表达，Hpz1 定位于细胞核。我们得出结论，Hpz1 调节 S 期的起始，并且可能在该功能中与 Rad3 合作。
