THO complex deficiency impairs DNA double-strand break repair via the RNA surveillance kinase SMG-1

Juliette A Kamp, Bennie B L G Lemmens*, Ron J Romeijn, Román González-Prieto, Jesper V Olsen, Alfred C O Vertegaal, Robin van Schendel, Marcel Tijsterman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)
29 Downloads (Pure)


The integrity and proper expression of genomes are safeguarded by DNA and RNA surveillance pathways. While many RNA surveillance factors have additional functions in the nucleus, little is known about the incidence and physiological impact of converging RNA and DNA signals. Here, using genetic screens and genome-wide analyses, we identified unforeseen SMG-1-dependent crosstalk between RNA surveillance and DNA repair in living animals. Defects in RNA processing, due to viable THO complex or PNN-1 mutations, induce a shift in DNA repair in dividing and non-dividing tissues. Loss of SMG-1, an ATM/ATR-like kinase central to RNA surveillance by nonsense-mediated decay (NMD), restores DNA repair and radio-resistance in THO-deficient animals. Mechanistically, we find SMG-1 and its downstream target SMG-2/UPF1, but not NMD per se, to suppress DNA repair by non-homologous end-joining in favour of single strand annealing. We postulate that moonlighting proteins create short-circuits in vivo, allowing aberrant RNA to redirect DNA repair.

Original languageEnglish
Pages (from-to)6235-6250
Number of pages16
JournalNucleic Acids Research
Issue number11
Publication statusPublished - 24 Jun 2022

Bibliographical note

© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.


Dive into the research topics of 'THO complex deficiency impairs DNA double-strand break repair via the RNA surveillance kinase SMG-1'. Together they form a unique fingerprint.

Cite this