| First Author | Abakir A | Year | 2020 |
| Journal | Nat Genet | Volume | 52 |
| Issue | 1 | Pages | 48-55 |
| PubMed ID | 31844323 | Mgi Jnum | J:305244 |
| Mgi Id | MGI:6707530 | Doi | 10.1038/s41588-019-0549-x |
| Citation | Abakir A, et al. (2020) N(6)-methyladenosine regulates the stability of RNA:DNA hybrids in human cells. Nat Genet 52(1):48-55 |
| abstractText | 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 cells(1-4). Here we show that N(6)-methyladenosine (m(6)A) modification, contributing to different aspects of messenger RNA metabolism(5,6), is detectable on the majority of RNA:DNA hybrids in human pluripotent stem cells. We demonstrate that m(6)A-containing R-loops accumulate during G2/M and are depleted at G0/G1 phases of the cell cycle, and that the m(6)A 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 gammaH2AX, a marker for DNA double-strand breaks, in mammalian cells. Our results suggest that m(6)A regulates accumulation of R-loops, implying a role for this modification in safeguarding genomic stability. |
