Abstract
Genome instability in yeast and mammals is caused by RNA-DNA hybrids that form as a result of defects in different aspects of RNA biogenesis. We report that in yeast mutants defective for transcription repression and RNA degradation, hybrid formation requires Rad51p and Rad52p. These proteins normally promote DNA-DNA strand exchange in homologous recombination. We suggest they also directly promote the DNA-RNA strand exchange necessary for hybrid formation since we observed accumulation of Rad51p at a model hybrid-forming locus. Furthermore, we provide evidence that Rad51p mediates hybridization of transcripts to homologous chromosomal loci distinct from their site of synthesis. This hybrid formation in trans amplifies the genome-destabilizing potential of RNA and broadens the exclusive co-transcriptional models that pervade the field. The deleterious hybrid-forming activity of Rad51p is counteracted by Srs2p, a known Rad51p antagonist. Thus Srs2p serves as a novel anti-hybrid mechanism in vivo. DOI:http://dx.doi.org/10.7554/eLife.00505.001.
Highlights
Genome instability can lead to a range of alterations in both the sequence and structure of chromosomes
We examined the effect of deleting RAD51 on hybrid formation and the associated genome instability in RNA biogenesis mutants of budding yeast
In this study we describe a compelling series of observations that demonstrate an in vivo role for Rad51p in promoting formation of RNA–DNA hybrids
Summary
Genome instability can lead to a range of alterations in both the sequence and structure of chromosomes While such changes may help drive evolution, more often they are associated with decreased organism fitness and increased susceptibility to disease (Aguilera and Gómez-González, 2008). Genome-wide screens in budding yeast and human cells have revealed that levels of RNA–DNA hybrids increase when RNA biogenesis is disturbed at sites of transcription initiation or repression, elongation, splicing, degradation, and export (Huertas and Aguilera, 2003; Li and Manley, 2005; Paulsen et al, 2009; Wahba et al, 2011; Stirling et al, 2012).
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