%0 Journal Article
%A Abakir, Abdulkadir
%A Giles, Tom C
%A Cristini, Agnese
%A Foster, Jeremy M
%A Dai, Nan
%A Starczak, Marta
%A Rubio-Roldan, Alejandro
%A Li, Miaomiao
%A Eleftheriou, Maria
%A Crutchley, James
%A Flatt, Luke
%A Young, Lorraine
%A Gaffney, Daniel J
%A Denning, Chris
%A Dalhus, Bjørn
%A Emes, Richard D
%A Gackowski, Daniel
%A Corrêa, Ivan R
%A Garcia-Perez, Jose L
%A Klungland, Arne
%A Gromak, Natalia
%A Ruzov, Alexey
%T N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells.
%D 2019
%U http://hdl.handle.net/10668/14837
%X R-loops are nucleic acid structures formed by an RNA:DNA hybrid and unpaired single-stranded DNA that represent a source of genomic instability in mammalian cells1-4. Here we show that N6-methyladenosine (m6A) modification, contributing to different aspects of messenger RNA metabolism5,6, is detectable on the majority of RNA:DNA hybrids in human pluripotent stem cells. We demonstrate that m6A-containing R-loops accumulate during G2/M and are depleted at G0/G1 phases of the cell cycle, and that the m6A reader promoting mRNA degradation, YTHDF2 (ref. 7), interacts with R-loop-enriched loci in dividing cells. Consequently, YTHDF2 knockout leads to increased R-loop levels, cell growth retardation and accumulation of γH2AX, a marker for DNA double-strand breaks, in mammalian cells. Our results suggest that m6A regulates accumulation of R-loops, implying a role for this modification in safeguarding genomic stability.
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