Abstract
Non-coding RNA (ncRNA) has recently emerged as a vital component of the DNA damage response (DDR), which was previously believed to be solely regulated by proteins. Many species of ncRNA can directly or indirectly influence DDR and enhance DNA repair, particularly in response to double-strand DNA breaks, which may hold therapeutic potential in the context of cancer. These include long non-coding RNA (lncRNA), microRNA, damage-induced lncRNA, DNA damage response small RNA, and DNA:RNA hybrid structures, which can be categorised as cis or trans based on the location of their synthesis relative to DNA damage sites. Mechanisms of RNA-dependent DDR include the recruitment or scaffolding of repair factors at DNA break sites, the regulation of repair factor expression, and the stabilisation of repair intermediates. DDR can also be communicated intercellularly via exosomes, leading to bystander responses in healthy neighbour cells to generate a population-wide response to damage. Many microRNA species have been directly implicated in the propagation of bystander DNA damage, autophagy, and radioresistance, which may prove significant for enhancing cancer treatment via radiotherapy. Here, we review recent developments centred around ncRNA and their contributions to intracellular and intercellular DDR mechanisms.
Highlights
Non-coding RNA has recently emerged as a vital component of the DNA damage response (DDR), which was previously believed to be solely regulated by proteins
These findings demonstrate that miRNA directly contributes to the fine-tuning of the DDR and DNA repair mechanisms via RNAi
In line with the previously stated role of miRNA species in transmitting radiation-induced bystander (RIBE) via exosomes, miR-6823-5p was identified as a candidate that is responsible for increased reactive oxygen species (ROS) and DNA damage in recipient cells as a result of SOD1 inhibition [123]
Summary
Eukaryotic cells are frequently exposed to external and endogenous insults that cause. Short- and long-range end resection are facilitated by MRN, CtIP, BRCA1, and EXO1/DNA2 to generate single-stranded DNA (ssDNA) overhangs These overhangs are protected by the immediate binding of RPA until BRCA2 mediates RPA displacement by RAD51 to form a nucleoprotein filament. NcRNA species that contribute to DNA repair, to that of DSBs, can be transcribed both proximally and distally to the site of DNA damage [1,5] As both can influence activity at the break site, they have been designated as cis and trans mechanisms of RNA-dependent DDR, respectively. We review recent developments in the rapidly growing field of RNA-dependent DDR, focusing on the contributions of cis and trans ncRNA species to intracellular DNA repair mechanisms as well as the effects of specific intercellular RNA transfer on DDR in both donor and recipient cells. It should be noted that there is some evidence for rRNA and tRNA involvement in DDR, these are not covered in this review
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