Suppression of non-homologous end joining does not rescue DNA repair defects in Fanconi anemia patient cells

Cell Cycle. 2020 Oct;19(19):2553-2561. doi: 10.1080/15384101.2020.1810394. Epub 2020 Aug 30.


Severe cellular sensitivity and aberrant chromosomal rearrangements in response to DNA interstrand crosslink (ICL) inducing agents are hallmarks of Fanconi anemia (FA) deficient cells. These phenotypes have previously been ascribed to inappropriate activity of non-homologous end joining (NHEJ) rather than a direct consequence of DNA ICL repair defects. Here we used chemical inhibitors, RNAi, and Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-Cas9 to inactivate various components of NHEJ in cells from FA patients. We show that suppression of DNA-PKcs, DNA Ligase IV, and 53BP1 is not capable of rescuing ICL-induced proliferation defects and only 53BP1 knockout partially suppresses the chromosomal abnormalities of FA patient cells.

Keywords: 53BP1; DNA-PKcs; FANCA; Fanconi anemia; KU70; KU80; LIGIV; mitomycin C; non-homologous end joining.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cell Line, Transformed
  • Cell Proliferation
  • DNA Damage*
  • DNA End-Joining Repair*
  • DNA Ligase ATP / genetics
  • DNA Ligase ATP / metabolism
  • Fanconi Anemia / genetics
  • Fanconi Anemia / metabolism*
  • Fanconi Anemia / pathology
  • Fanconi Anemia Complementation Group A Protein / genetics
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Fibroblasts / radiation effects
  • HCT116 Cells
  • Humans
  • Mutation
  • Tumor Suppressor p53-Binding Protein 1 / genetics
  • Tumor Suppressor p53-Binding Protein 1 / metabolism


  • CIB1 protein, human
  • Calcium-Binding Proteins
  • FANCA protein, human
  • Fanconi Anemia Complementation Group A Protein
  • LIG4 protein, human
  • TP53BP1 protein, human
  • Tumor Suppressor p53-Binding Protein 1
  • DNA Ligase ATP