Bushell paper.pdf (2.77 MB)
Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair
journal contribution
posted on 2023-06-09, 11:57 authored by Wei-Ting Lu, Ben R Hawley, George L Skalka, Robert A Baldock, Ewan M Smith, Aldo S Bader, M Malewicz, Felicity Watts, Ania Wilczynska, Martin BushellThe 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.
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Publication status
- Published
File Version
- Published version
Journal
Nature CommunicationsISSN
2041-1723Publisher
Nature Publishing GroupExternal DOI
Issue
532Volume
9Page range
1-13Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2018-02-07First Open Access (FOA) Date
2018-02-07First Compliant Deposit (FCD) Date
2018-02-07Usage metrics
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