DDX17 is required for efficient DSB repair at DNA:RNA hybrid deficient loci

Bader, A. S., Luessing, J., Hawley, B. R., Skalka, G. L., Lu, W.-T., Lowndes, N. F. and Bushell, M. (2022) DDX17 is required for efficient DSB repair at DNA:RNA hybrid deficient loci. Nucleic Acids Research, 50(18), pp. 10487-10502. (doi: 10.1093/nar/gkac843) (PMID:36200807) (PMCID:PMC9561282)

Abstract

Proteins with RNA-binding activity are increasingly being implicated in DNA damage responses (DDR). Additionally, DNA:RNA-hybrids are rapidly generated around DNA double-strand breaks (DSBs), and are essential for effective repair. Here, using a meta-analysis of proteomic data, we identify novel DNA repair proteins and characterise a novel role for DDX17 in DNA repair. We found DDX17 to be required for both cell survival and DNA repair in response to numerous agents that induce DSBs. Analysis of DSB repair factor recruitment to damage sites suggested a role for DDX17 early in the DSB ubiquitin cascade. Genome-wide mapping of R-loops revealed that while DDX17 promotes the formation of DNA:RNA-hybrids around DSB sites, this role is specific to loci that have low levels of pre-existing hybrids. We propose that DDX17 facilitates DSB repair at loci that are inefficient at forming DNA:RNA-hybrids by catalysing the formation of DSB-induced hybrids, thereby allowing propagation of the damage response.

• Item Type: Articles
• Additional Information: Cancer Research UK to the CRUK Beatson Institute [A17196 and A31287]; Bushell lab [A29252]; Science Foundation Ireland (http://www.sfi.ie/) FFP and IvP awards [19/FFP/6674 and 13/IA/1954 to N.F.L.]. Funding for open access charge: Cancer Research UK Core Funding.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bader, Aldo and Bushell, Professor Martin and Skalka, Dr George
• Authors: Bader, A. S., Luessing, J., Hawley, B. R., Skalka, G. L., Lu, W.-T., Lowndes, N. F., and Bushell, M.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nucleic Acids Research
• Publisher: Oxford University Press
• ISSN: 0305-1048
• ISSN (Online): 1362-4962
• Published Online: 06 October 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Nucleic Acids Research
• Publisher Policy: Reproduced under a Creative Commons License