RNA-binding protein RBM14 regulates dissociation and association of non-homologous end joining proteins

Cell Cycle. 2017 Jun 18;16(12):1175-1180. doi: 10.1080/15384101.2017.1317419. Epub 2017 Apr 20.

Abstract

Defects in the DNA damage response (DDR) are associated with multiple diseases, including cancers and neurodegenerative disorders. Emerging evidence indicates involvement of RNA-binding proteins (RBPs) in DDR. However, functions of RBPs in the DDR pathway remain elusive. We have shown previously that the RNA-binding protein RBM14 is required for non-homologous end joining (NHEJ). Here we show that RBM14 is required for efficient recruitment of XRCC4 and XLF to chromatin and the release of KU proteins from chromatin upon DNA damage. Failure of this process leads to accumulation of double-strand breaks (DSBs) in cells. Thus RBM14 plays crucial role in regulation of NHEJ upon DNA damage.

Keywords: DSB repair; NHEJ; RNA-binding protein.

MeSH terms

  • Cell Line, Tumor
  • DNA Breaks, Double-Stranded
  • DNA End-Joining Repair
  • DNA Repair Enzymes / metabolism
  • DNA-Activated Protein Kinase / metabolism
  • DNA-Binding Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Phosphorylation
  • Protein Binding
  • Protein Multimerization
  • Protein Processing, Post-Translational
  • Protein Transport

Substances

  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • NHEJ1 protein, human
  • RBM14 protein, human
  • XRCC4 protein, human
  • DNA-Activated Protein Kinase
  • DNA Repair Enzymes