Parallel Genome-Wide Screens Identify Synthetic Viable Interactions Between the BLM Helicase Complex and Fanconi Anemia

Nat Commun. 2017 Nov 1;8(1):1238. doi: 10.1038/s41467-017-01439-x.

Abstract

Maintenance of genome integrity via repair of DNA damage is a key biological process required to suppress diseases, including Fanconi anemia (FA). We generated loss-of-function human haploid cells for FA complementation group C (FANCC), a gene encoding a component of the FA core complex, and used genome-wide CRISPR libraries as well as insertional mutagenesis to identify synthetic viable (genetic suppressor) interactions for FA. Here we show that loss of the BLM helicase complex suppresses FANCC phenotypes and we confirm this interaction in cells deficient for FA complementation group I and D2 (FANCI and FANCD2) that function as part of the FA I-D2 complex, indicating that this interaction is not limited to the FA core complex, hence demonstrating that systematic genome-wide screening approaches can be used to reveal genetic viable interactions for DNA repair defects.

Publication types

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

MeSH terms

  • CRISPR-Cas Systems
  • Cell Line
  • DNA Damage
  • DNA Helicases / genetics
  • DNA Repair / genetics*
  • Fanconi Anemia / genetics*
  • Fanconi Anemia Complementation Group C Protein / genetics*
  • Fanconi Anemia Complementation Group D2 Protein / genetics
  • Fanconi Anemia Complementation Group Proteins / genetics
  • HEK293 Cells
  • Haploidy
  • Humans
  • Mutagenesis, Insertional
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • RecQ Helicases / genetics*

Substances

  • FANCC protein, human
  • FANCD2 protein, human
  • FANCI protein, human
  • Fanconi Anemia Complementation Group C Protein
  • Fanconi Anemia Complementation Group D2 Protein
  • Fanconi Anemia Complementation Group Proteins
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • Bloom syndrome protein
  • FANCM protein, human
  • DNA Helicases
  • RecQ Helicases