DNA helicases FANCM and DDX11 are determinants of PARP inhibitor sensitivity

DNA Repair (Amst). 2015 Feb:26:54-64. doi: 10.1016/j.dnarep.2014.12.003. Epub 2014 Dec 24.


The encouraging response rates of BRCA1- and BRCA2-mutated cancers toward PARP inhibitors make it worthwhile to identify other potential determinants of PARP inhibitor responsiveness. Since the Fanconi anemia (FA) pathway coordinates several DNA repair pathways, including homologous recombination in which BRCA1 and BRCA2 play important roles, we investigated whether this pathway harbors other predictors of PARP inhibitor sensitivity. Lymphoblastoid cell lines derived from individuals with FA or clinically related syndromes, such as Warsaw breakage syndrome, were tested for PARP inhibitor sensitivity. Remarkably, we found a strong variability in PARP inhibitor sensitivity among different FANCD1/BRCA2-deficient lymphoblasts, suggesting that PARP inhibitor response depends on the type of FANCD1/BRCA2 mutation. We identified the DNA helicases FANCM and DDX11 as determinants of PARP inhibitor response. These results may extend the utility of PARP inhibition as effective anticancer treatment.

Keywords: DDX11; FANCM; Fanconi anemia; PARP inhibitor; Sister chromatid cohesion; Warsaw breakage syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA2 Protein / genetics
  • Cell Line, Transformed
  • DEAD-box RNA Helicases / genetics*
  • DNA Helicases / genetics*
  • Enzyme Inhibitors / pharmacology*
  • Fanconi Anemia / genetics
  • Female
  • Fluorobenzenes / pharmacology
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Phthalazines / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors*


  • BRCA2 Protein
  • BRCA2 protein, human
  • Enzyme Inhibitors
  • Fluorobenzenes
  • KU0058948
  • Phthalazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • FANCM protein, human
  • DNA Helicases
  • DDX11 protein, human
  • DEAD-box RNA Helicases