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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.

Original publication

DOI

10.1016/j.molcel.2010.12.007

Type

Journal article

Journal

Mol Cell

Publication Date

07/01/2011

Volume

41

Pages

21 - 32

Keywords

DNA Damage, DNA Helicases, DNA Repair, Genomic Instability, Nucleic Acid Conformation, Nucleic Acid Hybridization, Protein Structure, Tertiary, RNA Helicases, Recombination, Genetic, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription, Genetic