Methylation of the central transcriptional regulator KLF4 by PRMT5 is required for DNA end resection and recombination

DNA Repair (Amst). 2020 Oct:94:102902. doi: 10.1016/j.dnarep.2020.102902. Epub 2020 Jun 27.


Cell fitness and survival upon exposure to DNA damage depends on the repair of DNA lesions. Interestingly, cellular identity does affect and finetunes such response, although the molecular basis of such differences between tissues and cell types is not well understood. Thus, a possibility is that DNA repair itself is controlled by the mechanisms that govern cell identity. Here we show that the KLF4, involved in cellular homeostasis, proliferation, cell reprogramming and cancer development, directly regulates resection and homologous recombination proficiency. Indeed, resection efficiency follows KLF4 protein levels, i.e. decreases upon KLF4 downregulation and increases when is overexpressed. Moreover, KLF4 role in resection requires its methylation by the methyl-transferase PRMT5. Thus, PRMT5 depletion not only mimics KLF4 downregulation, but also showed an epistatic genetic relationship. Our data support a model in which the methylation of KLF4 by PRMT5 is a priming event required to license DNA resection and homologous recombination.

Keywords: DNA end resection; DNA repair; KLF4; PRMT5; Recombination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA / metabolism
  • DNA Breaks, Double-Stranded
  • DNA End-Joining Repair*
  • Epistasis, Genetic*
  • Gene Expression Regulation
  • Humans
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Methylation
  • Protein Processing, Post-Translational*
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / metabolism*
  • Recombinational DNA Repair*


  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • DNA
  • PRMT5 protein, human
  • Protein-Arginine N-Methyltransferases