Arginine methylation of the DDX5 helicase RGG/RG motif by PRMT5 regulates resolution of RNA/DNA hybrids

ABSTRACT: Aberrant transcription-associated RNA:DNA hybrid (R-loop) formation often causes catastrophic conflicts during replication, resulting in DNA double-strand breaks and genomic instability. Preventing such conflicts requires hybrid dissolution by helicases and/or RNase H. Little is known about how such helicases are regulated. Herein, we identify DDX5, an RGG/RG motif-containing DEAD-box family RNA helicase, as crucial player in R-loop resolution. In vitro, recombinant DDX5 resolves R-loops in an ATP-dependent manner, leading to R-loop degradation by the XRN2 exoribonuclease. DDX5-deficient cells accumulate R-loops at loci with propensity to form such structures based on RNA:DNA immunoprecipitation (DRIP)-qPCR, causing spontaneous DNA double-strand breaks and hypersensitivity to replication s

SUBMITTER: Prof. Stephane Richard 

PROVIDER: S-SCDT-EMBOJ-2018-100986 | biostudies-other |

REPOSITORIES: biostudies-other