Journal
EMBO REPORTS
Volume 18, Issue 5, Pages 781-796Publisher
WILEY
DOI: 10.15252/embr.201643179
Keywords
5hmC; ATR; DNA damage response; DNA demethylation; TET3
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Funding
- Chinese Academy of Sciences [Y406541141, 1100050210]
- National Science Foundation of China (NSFC) [81471313, 91649119]
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An efficient, accurate, and timely DNA damage response (DDR) is crucial for the maintenance of genome integrity. Here, we report that ten-eleven translocation dioxygenase (TET) 3-mediated conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in response to ATR-dependent DDR regulates DNA repair. ATR-dependent DDR leads to dynamic changes in 5hmC levels and TET3 enzymatic activity. We show that TET3 is an ATR kinase target that oxidizes DNA during ATR-dependent DNA damage repair. Modulation of TET3 expression and activity affects DNA damage signaling and DNA repair and consequently cell death. Our results provide novel insight into ATR-mediated DDR, in which TET3-mediated DNA demethylation is crucial for efficient DNA repair and maintenance of genome stability.
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