Intrinsically disordered protein RBM14 plays a role in generation of RNA:DNA hybrids at double-strand break sites

Proc Natl Acad Sci U S A. 2020 Mar 10;117(10):5329-5338. doi: 10.1073/pnas.1913280117. Epub 2020 Feb 24.


Accumulating evidence suggests participation of RNA-binding proteins with intrinsically disordered domains (IDPs) in the DNA damage response (DDR). These IDPs form liquid compartments at DNA damage sites in a poly(ADP ribose) (PAR)-dependent manner. However, it is greatly unknown how the IDPs are involved in DDR. We have shown previously that one of the IDPs RBM14 is required for the canonical nonhomologous end joining (cNHEJ). Here we show that RBM14 is recruited to DNA damage sites in a PARP- and RNA polymerase II (RNAPII)-dependent manner. Both KU and RBM14 are required for RNAPII-dependent generation of RNA:DNA hybrids at DNA damage sites. In fact, RBM14 binds to RNA:DNA hybrids. Furthermore, RNA:DNA hybrids and RNAPII are detected at gene-coding as well as at intergenic areas when double-strand breaks (DSBs) are induced. We propose that the cNHEJ pathway utilizes damage-induced transcription and intrinsically disordered protein RBM14 for efficient repair of DSBs.

Keywords: DNA repair; RBM14; double-strand breaks.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chimera
  • DNA Breaks, Double-Stranded*
  • DNA End-Joining Repair*
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Intrinsically Disordered Proteins / metabolism*
  • Ku Autoantigen / metabolism
  • Nucleic Acid Hybridization
  • Protein Domains
  • RNA / genetics
  • RNA / metabolism*
  • RNA Polymerase II / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*


  • Intracellular Signaling Peptides and Proteins
  • Intrinsically Disordered Proteins
  • RBM14 protein, human
  • RNA-Binding Proteins
  • RNA
  • RNA Polymerase II
  • Ku Autoantigen