Sensing R-Loop-Associated DNA Damage to Safeguard Genome Stability
| Autor: | Maria Pia Longhese, Diego Bonetti, Carlo Rinaldi, Paolo Pizzul |
|---|---|
| Přispěvatelé: | Rinaldi, C, Pizzul, P, Longhese, M, Bonetti, D |
| Rok vydání: | 2020 |
| Předmět: |
Genome instability
R-loop DNA damage replication stress Review Biology Genome DSB 03 medical and health sciences chemistry.chemical_compound Cell and Developmental Biology 0302 clinical medicine Transcription (biology) replication stre lcsh:QH301-705.5 030304 developmental biology 0303 health sciences RNA Cell Biology R-loops Cell biology ATR chemistry lcsh:Biology (General) ATM Nucleic acid DSBs 030217 neurology & neurosurgery DNA Developmental Biology |
| Zdroj: | Frontiers in Cell and Developmental Biology Frontiers in Cell and Developmental Biology, Vol 8 (2021) |
| ISSN: | 2296-634X |
| Popis: | DNA transcription and replication are two essential physiological processes that can turn into a threat for genome integrity when they compete for the same DNA substrate. During transcription, the nascent RNA strongly binds the template DNA strand, leading to the formation of a peculiar RNA–DNA hybrid structure that displaces the non-template single-stranded DNA. This three-stranded nucleic acid transition is called R-loop. Although a programed formation of R-loops plays important physiological functions, these structures can turn into sources of DNA damage and genome instability when their homeostasis is altered. Indeed, both R-loop level and distribution in the genome are tightly controlled, and the list of factors involved in these regulatory mechanisms is continuously growing. Over the last years, our knowledge of R-loop homeostasis regulation (formation, stabilization, and resolution) has definitely increased. However, how R-loops affect genome stability and how the cellular response to their unscheduled formation is orchestrated are still not fully understood. In this review, we will report and discuss recent findings about these questions and we will focus on the role of ATM- and Rad3-related (ATR) and Ataxia–telangiectasia-mutated (ATM) kinases in the activation of an R-loop-dependent DNA damage response. |
| Databáze: | OpenAIRE |
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