Yeast Sen1 Helicase Protects the Genome from Transcription-Associated Instability

Sen1 of S. cerevisiae is a known component of the NRD complex implicated in transcription termination of nonpolyadenylated as well as some polyadenylated RNA polymerase II transcripts. We now show that Sen1 helicase possesses a wider function by restricting the occurrence of RNA:DNA hybrids that may naturally form during transcription, when nascent RNA hybridizes to DNA prior to its packaging into RNA protein complexes. These hybrids displace the nontranscribed strand and create R loop structures. Loss of Sen1 results in transient R loop accumulation and so elicits transcription-associated recombination. SEN1 genetically interacts with DNA repair genes, suggesting that R loop resolution requires proteins involved in homologous recombination. Based on these findings, we propose that R loop formation is a frequent event during transcription and a key function of Sen1 is to prevent their accumulation and associated genome instability. [Display omitted] ► Nascent RNA forms hybrids with underwound DNA upstream of elongating Pol II ► Single-stranded DNA so formed is prone to damage which results in genome instability ► Sen1 helicase acts to remove R loops by resolving RNA:DNA hybrids ► Sen1 function in Pol II elongation and termination may relate to R loop resolution