TET3-mediated DNA oxidation promotes ATR-dependent DNA damage response

发布日期2017-09-25 08:53 来源:本站

TET3-mediated DNA oxidation promotes ATR-dependent DNA damage response

Dewei Jiang1, Shu Wei1,2, Fei Chen1, Ying Zhang1 & Jiali Li1,3,*

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.