About this Research Topic

Background

The genome is constantly exposed to both endogenous and exogenous sources of damage, with DNA double-strand breaks (DSBs) being among the most harmful DNA lesions. In consequence, there are an ample variety of factors involved in ensuring the accurate and timely repair of breaks throughout the cell cycle. Recent evidence supports that the context in which breaks occur can somehow affect the outcome of the repair mechanisms. In particular, the potential impact by RNA molecules is emerging to be a new fascinating and controversial field of study. Because transcription is an essential process that constantly generates RNA transcripts for protein synthesis, RNA interference pathways, as well as non-coding RNAs, which can reanneal with the DNA template to form DNA-RNA hybrids, it makes these transcribed regions a hot bed for DNA DSBs. The influence of RNA in repair mechanisms could greatly vary in different cell types and lineages, between terminally differentiated cells (such as neurons) and rapidly dividing cancerous cells. Hence, it is critical to dissect the effect of RNA in repair pathways for understanding the mechanisms of pathogenesis of several neurodegenerative diseases as well as cancers.

The repair of DNA breaks has been traditionally studied in the context of the DNA and a vast amount of research during the last decades has enabled us to have a quite complete picture of the different mechanisms and factors that participate and regulate DNA repair via non-homologous end joining (NHEJ) and homologous recombination (HR) pathways. However, the interference of the RNA metabolism with DNA repair mechanisms has only just started to emerge. When DNA breaks occur along transcribed regions, several aspects are to be considered to ensure accurate repair and the maintenance of genomic stability. Among them, evidence supports that DNA-RNA hybridization is promoted by DNA breakage. Interestingly, nascent RNAs have also been shown to partake in and regulate DNA repair and RNAs are involved in various regulatory mechanisms in cells, including the DNA damage response. RNA biogenesis factors, epigenetic signaling, and motor proteins that unwind DNA-RNA hybrids have been associated with mitigating DNA-RNA hybrids in human cells, although the current literature seems to be just the tip of the iceberg.

This project aims to gather the view of researchers from the DNA damage response and the RNA metabolism fields about the existing literature that has uncovered the intimate relationship between RNA and DNA repair, as well as to shed light on future perspectives of research in order to acquire a complete view on how the presence of RNA could influence various steps of DSB repair – resection, annealing, gap-filling, strand exchange, and end joining, and transcription-coupled repair processes, which could be exerted by recruitment of DNA repair factors via direct interaction or phase-separation.

In this current Research Topic, we are looking forward to receiving original research articles, brief research reports, reviews/mini reviews, perspectives and opinions that could shed light on the interplay between RNA metabolism and DNA repair pathways. These articles may include but are not limited to following topics:

• Factors associated with prevention or mitigation of DNA-RNA hybrids at DNA double strand breaks (DSBs)
• Epigenetic marks influencing DSB repair
• Roles of RNAs in the DNA damage response
• Biochemical mechanisms associated with RNA-regulated DNA repair processes
• RNA-guided DNA repair mechanisms for DSBs at collapsed replication forks
• Transcription-coupled repair mechanisms
• Molecular tools to map RNAs at DSBs
• RNA-metabolism associated diseases

Keywords: DNA damage repair, Genome stability, R-loop, Transcription

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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