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UV‐induced activation of ATR is mediated by UHRF2
Author(s) -
Hanaki Shunsuke,
Habara Makoto,
Shimada Midori
Publication year - 2021
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12851
Subject(s) - biology , dna damage , histone , microbiology and biotechnology , dna methylation , dna , ring finger , cell culture , phosphorylation , epigenetics , cell growth , biochemistry , gene , genetics , gene expression
Abstract 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.