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Series GSE113580 Query DataSets for GSE113580
Status Public on Jun 27, 2018
Title Yra1-bound R loops cause orientation-independent transcription-replication collisions and telomere instability
Organism Saccharomyces cerevisiae
Experiment type Other
Summary R loops are an important source of genome instability largely due to its negative impact on replication progression. Yra1/ALY is an abundant RNA-binding factor conserved from yeast to humans and required for mRNA export, but its excess cause lethality and genome instability. Here, we show that Yra1 binds RNA-DNA hybrids in vitro and when artificially overexpressed is recruited to chromatin in an RNA-DNA hybrid-dependent manner stabilizing R loops and converting them into replication obstacles in vivo. Importantly, excess of Yra1 increases R loop-mediated genome instability caused by transcription-replication collisions regardless of whether they are co-directional or head-on. It also induces telomere shortening and senescence, consistent with a defect in telomere replication. Our results indicate that R loops form transiently in cells regardless of replication and, after stabilization by excess Yra1, they compromise genome integrity, in agreement with a two-step model of R loop-mediated genome instability. This work opens new perspectives to understand transcription-associated genome instability in repair-deficient cells, including tumoral cells.
 
Overall design RNA:DNA hybrid immunoprecipitation sequencing (DRIP-seq) in wild-type yeast cells
 
Contributor(s) Lafuente-Barquero JF, Aguilera A
Citation(s) 29954833
Submission date Apr 24, 2018
Last update date Sep 26, 2018
Contact name Andrés Aguilera
Organization name CABIMER, Universidad de Sevilla
Department Genome BIology
Lab Genome Instability & Cancer
Street address Av. Américo Vespucio 24
City Seville
ZIP/Postal code 41092
Country Spain
 
Platforms (1)
GPL16028 Ion Torrent PGM (Saccharomyces cerevisiae)
Samples (2)
GSM3109274 WildType_DRIP-seq_IP
GSM3109275 WildType_DRIP-seq_INP
Relations
BioProject PRJNA453145
SRA SRP142458

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Supplementary file Size Download File type/resource
GSE113580_RAW.tar 7.6 Mb (http)(custom) TAR (of BED, BW)
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Raw data are available in SRA
Processed data provided as supplementary file

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