Jack of all trades? The versatility of RNA in DNA double-strand break repair

Abstract

<jats:title>Abstract</jats:title> <jats:p>The mechanisms by which RNA acts in the DNA damage response (DDR), specifically in the repair of DNA double-strand breaks (DSBs), are emerging as multifaceted and complex. Different RNA species, including but not limited to; microRNA (miRNA), long non-coding RNA (lncRNA), RNA:DNA hybrid structures, the recently identified damage-induced lncRNA (dilncRNA), damage-responsive transcripts (DARTs), and DNA damage-dependent small RNAs (DDRNAs), have been shown to play integral roles in the DSB response. The diverse properties of these RNAs, such as sequence, structure, and binding partners, enable them to fulfil a variety of functions in different cellular contexts. Additionally, RNA can be modified post-transcriptionally, a process which is regulated in response to cellular stressors such as DNA damage. Many of these mechanisms are not yet understood and the literature contradictory, reflecting the complexity and expansive nature of the roles of RNA in the DDR. However, it is clear that RNA is pivotal in ensuring the maintenance of genome integrity. In this review, we will discuss and summarise recent evidence which highlights the roles of these various RNAs in preserving genomic integrity, with a particular focus on the emerging role of RNA in the DSB repair response.</jats:p>

New Faces of old Friends: Emerging new Roles of RNA-Binding Proteins in the DNA Double-Strand Break Response

“…While it has long been known that the processing and transport of protein-coding mRNAs is crucial for the DSB response (Wickramasinghe and Venkitaraman, 2016), long and short non-coding RNAs have only recently been identified as direct regulators of this pathway. Indeed, the last years have seen the identification of an evergrowing network of diverse non-coding RNA species that locally modulate DSB signaling and repair (Mikolaskova et al, 2018;Bader et al, 2020;Ketley and Gullerova, 2020). Not surprisingly, the RNA network surrounding the DSB response is tightly associated with RNA-binding proteins (RBPs), many of which are themselves subject to DNA damage-induced PTMs (Matsuoka et al, 2007;Paulsen et al, 2009;Bensimon et al, 2010;Hurov et al, 2010;Słabicki et al, 2010;Adamson et al, 2012;Beli et al, 2012;Izhar et al, 2015;Shkreta and Chabot, 2015).…”

The Emerging Role of RNA Modifications in DNA Double-Strand Break Repair

“…Recently, it has become clear that RNA modifications also affect DNA repair ( Ketley and Gullerova, 2020 ) ( Table 1 ). The first example was the role of m6A RNA methylation in the repair of DNA damage induced by UV facilitating the rapid recruitment of Pol κ to UV-induced DNA damage ( Xiang et al, 2017 ).…”

Sweet Melody or Jazz? Transcription Around DNA Double-Strand Breaks

“…DSBs are considered the most lethal lesions, leading to chromosome rearrangements and deletions and, consequently, to oncogenesis or cell death. The common sources of DNA damage include ionic radiation (IR), ultraviolet radiation, x-rays, redox oxygen species, chemotherapeutic drugs, and stalled replication fork (Ciccia and Elledge, 2010;Ketley and Gullerova, 2020). To counteract these pernicious cellular and external activities, DNA damage response (DDR) pathways developed to safeguard genomic fidelity by facilitating lesion site recognition, DNA damage repair, or DNA damage tolerance (DDT) (Ciccia and Elledge, 2010;Branzei and Psakhye, 2016) (Figure 1A).…”

“…RNAs can be simply categorized into messenger RNAs (mRNAs) with encoding information for protein production and noncoding RNAs (ncRNAs). Depending on their length and origin, long ncRNAs (lncRNAs, >200 bp) and small ncRNAs (sncRNAs, <200 bp) can be further processed into microRNAs (miRNAs) and other types of RNAs exhibiting versatility in DDR (Ketley and Gullerova, 2020). miRNAs are reported to regulate gene expression by post-transcriptional gene silencing by targeting mRNAs of various key proteins involved in DDR (Van Kouwenhove et al, 2011).…”