Yeast Sen1 helicase protects the genome from transcription-associated instability

TY - JOUR

T1 - Yeast Sen1 helicase protects the genome from transcription-associated instability

AU - Mischo, Hannah E

AU - Gómez-González, Belén

AU - Grzechnik, Pawel

AU - Rondón, Ana G

AU - Wei, Wu

AU - Steinmetz, Lars

AU - Aguilera, Andrés

AU - Proudfoot, Nick J

N1 - Copyright © 2011 Elsevier Inc. All rights reserved.

PY - 2011/1/7

Y1 - 2011/1/7

N2 - 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.

AB - 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.

KW - DNA Damage

KW - DNA Helicases/genetics

KW - DNA Repair/genetics

KW - Genomic Instability

KW - Nucleic Acid Conformation

KW - Nucleic Acid Hybridization

KW - Protein Structure, Tertiary

KW - RNA Helicases/genetics

KW - Recombination, Genetic

KW - Saccharomyces cerevisiae/genetics

KW - Saccharomyces cerevisiae Proteins/genetics

KW - Transcription, Genetic

U2 - 10.1016/j.molcel.2010.12.007

DO - 10.1016/j.molcel.2010.12.007

M3 - Article

C2 - 21211720

SN - 1097-2765

VL - 41

SP - 21

EP - 32

JO - MOLECULAR CELL

JF - MOLECULAR CELL

IS - 1

ER -