Multiple exogenous and endogenous genotoxic agents threaten the integrity of the genome, but one major source of spontaneous DNA damage is the formation of unscheduled DNA–RNA hybrids. These can be genetically detected by their ability to induce recombination. The origin of spontaneous hybrids has been mainly attributed to the nascent RNA formed co-transcriptionally in cis invading its own DNA template. However, it was unclear whether hybrids could also be spontaneously generated by RNA produced in a different locus (in trans). Using new genetic systems in the yeast Saccharomyces cerevisiae, we recently tested whether hybrids could be formed in trans and compromise genome integrity. Whereas we detected recombinogenic DNA–RNA hybrids in cis and in a Rad51-independent manner, we found no evidence for recombinogenic DNA–RNA hybrids to be formed with RNAs produced in trans. Here, we further discuss the implications in the field for the origin of genetic instability and the threats coming from RNAs.

多种外源性和内源性遗传毒性剂威胁着基因组的完整性，但是自发性DNA损伤的一个主要来源是计划外的DNA-RNA杂种的形成。这些可以通过它们诱导重组的能力进行遗传检测。自发杂种的起源主要归因于顺式侵入其自身DNA模板的共转录形成的新生RNA 。但是，尚不清楚杂种是否也可以由在不同基因座（反式）产生的RNA自发产生。最近，我们在酿酒酵母中使用了新的遗传系统，测试了杂种是否可以反式形成并损害基因组完整性。鉴于我们检测到了重组DNA-RNA杂种以顺式和不依赖Rad51的方式，我们没有发现与反式产生的RNA形成重组DNA-RNA杂种的证据。在这里，我们进一步讨论了该领域对于遗传不稳定性起源和来自RNA的威胁的影响。