UHRF1 (Ubiquitin-like with PHD and ring finger domains 1) regulates DNA methylation and histone modifications and plays a key role in cell proliferation and the DNA damage response. However, the function of UHRF2, a paralog of UHRF1, in the DNA damage response remains largely unknown. Here, we show that UHRF2 is essential for maintaining cell viability after UV irradiation, as well as for the proliferation of cancer cells. UHRF2 was found to physically interact with ATR in a DNA damage-dependent manner through UHRF2’s TTD domain. In addition, phosphorylation of threonine at position 1989, which is required for UV-induced activation of ATR, was impaired in cells depleted of UHRF2, suggesting that UHRF2 is essential in ATR activation. In conclusion, these results suggest a new regulatory mechanism of ATR activation mediated by UHRF2.

中文翻译：

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紫外线诱导的 ATR 激活由 UHRF2 介导

UHRF1（泛素样与 PHD 和无名指结构域 1）调节 DNA 甲基化和组蛋白修饰，并在细胞增殖和 DNA 损伤反应中起关键作用。然而，UHRF2（UHRF1 的旁系同源物）在 DNA 损伤反应中的功能在很大程度上仍然未知。在这里，我们表明 UHRF2 对于维持紫外线照射后的细胞活力以及癌细胞的增殖至关重要。发现 UHRF2 通过 UHRF2 的 TTD 域以 DNA 损伤依赖性方式与 ATR 物理相互作用。此外，UV 诱导的 ATR 激活所需的 1989 位苏氨酸磷酸化在耗尽 UHRF2 的细胞中受损，表明 UHRF2 在 ATR 激活中是必不可少的。总之，这些结果表明了由 UHRF2 介导的 ATR 激活的新调节机制。