UV-induced activation of ATR is mediated by UHRF2.
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.
Mesh Terms:
Ataxia Telangiectasia Mutated Proteins, Cell Death, Cell Line, Tumor, Cell Proliferation, Checkpoint Kinase 1, DNA Damage, Humans, Protein Binding, Ubiquitin-Protein Ligases, Ultraviolet Rays
Ataxia Telangiectasia Mutated Proteins, Cell Death, Cell Line, Tumor, Cell Proliferation, Checkpoint Kinase 1, DNA Damage, Humans, Protein Binding, Ubiquitin-Protein Ligases, Ultraviolet Rays
Genes Cells
Date: Jun. 01, 2021
PubMed ID: 33848395
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