title: Yeast Sen1 helicase protects the genome from transcription-associated instability.
abstract: 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.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Mischo
authors.forename: Belén
authors.initials: B
authors.lastname: Gómez-González
authors.forename: Pawel
authors.initials: P
authors.lastname: Grzechnik
authors.forename: Ana G
authors.initials: AG
authors.lastname: Rondón
authors.forename: Wu
authors.initials: W
authors.lastname: Wei
authors.forename: Lars
authors.initials: L
authors.lastname: Steinmetz
authors.forename: Andrés
authors.initials: A
authors.lastname: Aguilera
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Proudfoot
mesh_terms: D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics; D042822:Genomic Instability; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C542347:SEN1 protein, S cerevisiae; D004265:DNA Helicases; D020365:RNA Helicases