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

Lu, W.-T., Hawley, B. R., Skalka, G. L., Baldock, R. A., Smith, E. M., Bader, A. S., Malewicz, M., Watts, F. Z., Wilczynska, A. and Bushell, M. (2018) Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair. Nature Communications, 9, 532. (doi: 10.1038/s41467-018-02893-x) (PMID:29416038) (PMCID:PMC5803274)

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.

• Item Type: Articles
• Additional Information: This work was funded by Medical Research Council (MRC). W.-T.L. was partially supported by an MRC Centenary Award. A.W. is funded by the BBSRC.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Skalka, Dr George and Bushell, Professor Martin
• Authors: Lu, W.-T., Hawley, B. R., Skalka, G. L., Baldock, R. A., Smith, E. M., Bader, A. S., Malewicz, M., Watts, F. Z., Wilczynska, A., and Bushell, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Nature Communications 9: 532
• Publisher Policy: Reproduced under a Creative Commons License