About this Research Topic
DNA double strand breaks (DSBs) are induced upon cellular exposure to ionizing radiation (IR), radiomimetic compounds and reactive oxygen species and they account for most of the damaged DNA. Consequently, the cells elicit an elaborate signalling network, known as DNA damage response (DDR), to detect and repair these cytotoxic lesions. The DDR serves as an anti-tumour barrier since it guards against genome instability and activated oncogenes. Indeed, DDR activation leads to premature senescence as consequence of oncogene expression through a process known as Oncogene Induced Senescence (OIS).
The induction of the DDR pathway entails the activation of multiple protein kinases and results in the repair of DSBs via error-prone nonhomologous end-joining (NHEJ) or high-fidelity homologous recombination repair (HRR). In addition to the canonical networks, the DDR is also epigenetically regulated. Indeed, at sites of DNA damage, a number of chromatin-modifying events occur. DDR affects post-translational modifications (PTMs) on chromatin thus altering the cellular transcriptional program. Orchestrating spatial and temporal patterns of gene expression in the context of DNA damage may rely on non-coding RNAs. Small regulatory RNAs, known as miRNAs, are regulated transcriptionally and post-transcriptionally in the DDR thus targeting DNA damage responsive genes. On the other side, it has been suggested that long non-coding RNAs may modulate the DDR by driving changes in chromatin architecture thus functioning as molecular scaffolds of chromatin-remodeling complexes as well as of transcription factors.
This Research Topic is aimed at comprehensive investigations of basic and novel mechanisms that underlie the DNA damage response in eukaryotes. Special emphasis will be given to the emerging crosstalk between non-coding RNAs, chromatin and transcription in the context of DNA damage.
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