Abstract
In the last decade, it has become evident that RNA is frequently found in DNA. It is now well established that single embedded ribonucleoside monophosphates (rNMPs) are primarily introduced by DNA polymerases and that longer stretches of RNA can anneal to DNA, generating RNA:DNA hybrids. Among them, the most studied are R-loops, peculiar three-stranded nucleic acid structures formed upon the re-hybridization of a transcript to its template DNA. In addition, polyribonucleotide chains are synthesized to allow DNA replication priming, double-strand breaks repair, and may as well result from the direct incorporation of consecutive rNMPs by DNA polymerases. The bright side of RNA into DNA is that it contributes to regulating different physiological functions. The dark side, however, is that persistent RNA compromises genome integrity and genome stability. For these reasons, the characterization of all these structures has been under growing investigation. In this review, we discussed the origin of single and multiple ribonucleotides in the genome and in the DNA of organelles, focusing on situations where the aberrant processing of RNA:DNA hybrids may result in multiple rNMPs embedded in DNA. We concluded by providing an overview of the currently available strategies to study the presence of single and multiple ribonucleotides in DNA in vivo.
Highlights
The presence of single ribonucleotides in DNA has been extensively studied and reported in many excellent reviews [1,2,3,4]; here, we just recalled some important details about their sources, effects, and removal
Most of the published literature about RNA:DNA hybrids focus on R-loops, but the world of RNA:DNA hybrids is much wider: it includes RNA primers found at Okazaki fragments, hybrids formed at double-strand breaks (DSBs), polyribonucleotide stretches eventually incorporated by DNA polymerases, etc
Different models for mitochondrial DNA duplication have been proposed, which are well described in recent reviews [152,153]; here, we only summarized the types and the sources of ribonucleoside monophosphates (rNMPs) that could be found into mtDNA
Summary
The presence of single ribonucleotides in DNA has been extensively studied and reported in many excellent reviews [1,2,3,4]; here, we just recalled some important details about their sources, effects, and removal. We still lack a complete understanding of the different types of multiple rNMPs that can be found in DNA. Most of the published literature about RNA:DNA hybrids focus on R-loops, but the world of RNA:DNA hybrids is much wider: it includes RNA primers found at Okazaki fragments, hybrids formed at double-strand breaks (DSBs), polyribonucleotide stretches eventually incorporated by DNA polymerases, etc. We discussed with particular interest the possible sources and consequences of inserting multiple rNMPs into DNA. 2. DNA Polymerases are the Main Source of Single Ribonucleotides Introduced in DNA
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