Both prokaryotes and eukaryotes store genetic information in DNA rather than RNA. The primary reason for this preferential use of deoxynucleotide triphosphates (dNTPs) over ribonucleotide triphosphates (rNTPs) as the building block to store genetic information is attributed to the instability of RNA. The presence of the 2’-hydroxyl (OH) group on the ribose moiety of RNA is chemically reactive, and may induce spontaneous hydrolysis of the sugar phosphate backbone. Over the last two decades, an increasing body of work has suggested that the role of RNA on the metabolism and maintenance of DNA has been generally underestimated. For example, it has been found that, during DNA replication, RNA is incorporated into DNA at the rate of 0.1-1 ribonucleotide for each kilobase of synthesized deoxyribonucleotides [1]. Moreover, during transcription the produced RNA can remain annealed to one of the DNA strands, forming a three-stranded nucleic acid structure called an R-loop. Unexpectedly, R-loops are highly prevalent, and can potentially cover nearly 5% of a mammalian genome [2]. Both of these processes impact genome stability, in negative as well as potentially positive ways. In this review, we will consider these two opposing aspects of RNA in relation to DNA repair. First, we will cover the role of incorporated RNA, specifically genomic ribonucleotides, as a possible threat to genome stability. Unscheduled R-loops are also important to consider as potentially detrimental to the integrity of the genome; however, we refer the reader to several excellent recent reviews on this topic (for example, [3], [4]), and we therefore will not cover this specific area here. Second, we will consider the mechanisms of incorporated ribonucleotides, R-loops, RNA modifications, and transcribed RNAs as potentially useful in promoting or signaling of specific DNA repair processes.
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