Drugging the R-loop interactome: RNA-DNA hybrid binding proteins as targets for cancer therapy

Beáta Boros-Oláh, Nikoletta Dobos, Lilla Hornyák, Zoltán Szabó, Zsolt Karányi, Gábor Halmos, Jason Roszik, Lóránt Székvölgyi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Unravelling the origin of genetic alterations from point mutations to chromosomal rearrangements was greatly enhanced by the discovery of RNA-DNA hybrids (R-loops) that behave as hotspots of genomic instability in a variety of organisms. Current models suggest that uncontrolled R-loops are a hazard to genome integrity, therefore, identifying proteins that are involved in recognising and signalling R-loop structures are of key importance. Herein we analysed key RNA-DNA hybrid binding proteins in humans taking advantage of large-scale gene expression, survival rate, and drug-sensitivity data from cancer genomics databases. We show that expression of RNA-DNA hybrid binding proteins in various cancer types is associated with survival and may have contrasting outcomes in responding to therapeutic treatments. Based on the revealed pharmacogenomic landscape of human RNA-DNA hybrid binding proteins, we propose that R-loops and R-loop binding proteins are potentially relevant new epigenetic markers and therapeutic targets in multiple cancers.

Original languageEnglish
Article number102642
JournalDNA Repair
Volume84
DOIs
Publication statusPublished - Dec 2019

Keywords

  • Cancer diagnostics and therapy
  • Chemotherapy
  • Clinical trial
  • Drug sensitivity
  • R-loop
  • RNA-DNA hybrid
  • Survival association

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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