Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair

Wei-Ting Lu, Ben R Hawley, George L Skalka, Robert A Baldock, Ewan M Smith, Aldo S Bader, Michal Malewicz, Felicity Z Watts, Ania Wilczynska, Martin Bushell

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)532
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018
Externally publishedYes

Fingerprint

DNA Breaks
DNA Repair
Repair
deoxyribonucleic acid
RNA
DNA
DNA Damage
Ribonuclease III
damage
RNA Sequence Analysis
Recombinational DNA Repair
Double-Stranded DNA Breaks
Cells
MicroRNAs
DNA Sequence Analysis
biological evolution
sequencing
Cell Survival
Joining
enzymes

Cite this

Lu, Wei-Ting ; Hawley, Ben R ; Skalka, George L ; Baldock, Robert A ; Smith, Ewan M ; Bader, Aldo S ; Malewicz, Michal ; Watts, Felicity Z ; Wilczynska, Ania ; Bushell, Martin. / Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair. In: Nature Communications. 2018 ; Vol. 9, No. 1. pp. 532.
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Lu, W-T, Hawley, BR, Skalka, GL, Baldock, RA, Smith, EM, Bader, AS, Malewicz, M, Watts, FZ, Wilczynska, A & Bushell, M 2018, 'Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair' Nature Communications, vol. 9, no. 1, pp. 532. https://doi.org/10.1038/s41467-018-02893-x

Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair. / Lu, Wei-Ting; Hawley, Ben R; Skalka, George L; Baldock, Robert A; Smith, Ewan M; Bader, Aldo S; Malewicz, Michal; Watts, Felicity Z; Wilczynska, Ania; Bushell, Martin.

In: Nature Communications, Vol. 9, No. 1, 01.12.2018, p. 532.

Research output: Contribution to journalArticle

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AU - Bader, Aldo S

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AU - Watts, Felicity Z

AU - Wilczynska, Ania

AU - Bushell, Martin

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