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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
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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.
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Overall design |
RNA:DNA hybrid immunoprecipitation sequencing (DRIP-seq) in wild-type yeast cells
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Contributor(s) |
Lafuente-Barquero JF, Aguilera A |
Citation(s) |
29954833 |
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Submission date |
Apr 24, 2018 |
Last update date |
Sep 26, 2018 |
Contact name |
Andrés Aguilera |
Organization name |
CABIMER, Universidad de Sevilla
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Department |
Genome BIology
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Lab |
Genome Instability & Cancer
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Street address |
Av. Américo Vespucio 24
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City |
Seville |
ZIP/Postal code |
41092 |
Country |
Spain |
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Platforms (1) |
GPL16028 |
Ion Torrent PGM (Saccharomyces cerevisiae) |
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Samples (2) |
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Relations |
BioProject |
PRJNA453145 |
SRA |
SRP142458 |
Supplementary file |
Size |
Download |
File type/resource |
GSE113580_RAW.tar |
7.6 Mb |
(http)(custom) |
TAR (of BED, BW) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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