Department of Pharmacology, DNA Repair Research Center, Chosun University School of Medicine, 375 Seosuk-Dong, Gwangju 501-759, Republic of Korea.
Biochem Biophys Res Commun. 2011 Jan 7;404(1):476-81. doi: 10.1016/j.bbrc.2010.12.005. Epub 2010 Dec 6.
Several recent studies have shown that protein phosphatase 5 (PP5) participates in cell cycle arrest after DNA damage, but its roles in DNA repair have not yet been fully characterized. We investigated the roles of PP5 in the repair of ultraviolet (UV)- and neocarzinostatin (NCS)-induced DNA damage. The results of comet assays revealed different repair patterns in UV- and NCS-exposed U2OS-PS cells. PP5 is only essential for Rad3-related (ATR)-mediated DNA repair. Furthermore, the phosphorylation of 53BP1 and BRCA1, important mediators of DNA damage repair, and substrates of ATR and ATM decreased in U2OS-PS cells exposed to UV radiation. In contrast, the cell cycle arrest proteins p53, CHK1, and CHK2 were normally phosphorylated in U2OS and U2OS-PS cells exposed to UV radiation or treated with NCS. In view of these results, we suggest that PP5 plays a crucial role in ATR-mediated repair of UV-induced DNA damage.
几项最近的研究表明，蛋白磷酸酶 5（PP5）参与 DNA 损伤后的细胞周期停滞，但它在 DNA 修复中的作用尚未得到充分表征。我们研究了 PP5 在紫外线（UV）和新制癌菌素（NCS）诱导的 DNA 损伤修复中的作用。彗星试验的结果显示，在 UV 和 NCS 暴露的 U2OS-PS 细胞中，修复模式不同。PP5 仅对 Rad3 相关（ATR）介导的 DNA 修复是必需的。此外，ATR 和 ATM 的重要介质 53BP1 和 BRCA1 的磷酸化以及 ATR 和 ATM 的底物在暴露于 UV 辐射的 U2OS-PS 细胞中减少。相比之下，在 U2OS 和 U2OS-PS 细胞中，正常地对 UV 辐射或 NCS 处理进行了细胞周期停滞蛋白 p53、CHK1 和 CHK2 的磷酸化。鉴于这些结果，我们认为 PP5 在 ATR 介导的 UV 诱导的 DNA 损伤修复中起着至关重要的作用。
