Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair
| Autor: | Aldo S. Bader, Wei-Ting Lu, Michal Malewicz, Ania Wilczynska, Robert A Baldock, Ewan M. Smith, Martin Bushell, Ben R Hawley, George Skalka, Felicity Z. Watts |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Ribonuclease III DNA End-Joining Repair DNA Repair DNA damage DNA repair Science General Physics and Astronomy Q1 General Biochemistry Genetics and Molecular Biology Article DEAD-box RNA Helicases 03 medical and health sciences chemistry.chemical_compound Cell Line Tumor Humans DNA Breaks Double-Stranded Homologous Recombination QH426 Drosha Multidisciplinary biology Gene Expression Profiling RNA General Chemistry DNA Cell biology 030104 developmental biology chemistry A549 Cells biology.protein RNA Interference Homologous recombination Dicer DNA Damage |
| Zdroj: | Nature Communications Nature Communications, Vol 9, Iss 1, Pp 1-13 (2018) |
| ISSN: | 2041-1723 |
| Popis: | The error-free and efficient repair of DNA double-stranded breaks (DSBs) is extremely important for cell survival. RNA has been implicated in the resolution of DNA damage but the mechanism remains poorly understood. Here, we show that miRNA biogenesis enzymes, Drosha and Dicer, control the recruitment of repair factors from multiple pathways to sites of damage. Depletion of Drosha significantly reduces DNA repair by both homologous recombination (HR) and non-homologous end joining (NHEJ). Drosha is required within minutes of break induction, suggesting a central and early role for RNA processing in DNA repair. Sequencing of DNA:RNA hybrids reveals RNA invasion around DNA break sites in a Drosha-dependent manner. Removal of the RNA component of these structures results in impaired repair. These results show how RNA can be a direct and critical mediator of DNA damage repair in human cells. The mechanism through which Drosha and Dicer affect DNA repair is not clear. Here the authors use a high-throughput approach to uncover the role of Drosha in promoting DNA:RNA hybrids at DNA damaged sites. |
| Databáze: | OpenAIRE |
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