DOG-1 is the Caenorhabditis elegans BRIP1/FANCJ homologue and functions in interstrand cross-link repair

Mol Cell Biol. 2008 Mar;28(5):1470-9. doi: 10.1128/MCB.01641-07. Epub 2007 Dec 17.


Fanconi anemia (FA) is a cancer susceptibility syndrome characterized by defective DNA interstrand cross-link (ICL) repair. Here, we show that DOG-1 is the Caenorhabditis elegans homologue of FANCJ, a helicase mutated in FA-J patients. DOG-1 performs a conserved role in ICL repair, as dog-1 mutants are hypersensitive to ICL-inducing agents, but not to UVC irradiation or X rays. Genetic analysis indicated that dog-1 is epistatic with fcd-2 (C. elegans FANCD2) but is nonepistatic with brc-1 (C. elegans BRCA1), thus establishing the existence of two distinct pathways of ICL repair in worms. Furthermore, DOG-1 is dispensable for FCD-2 and RAD-51 focus formation, suggesting that DOG-1 operates downstream of FCD-2 and RAD-51 in ICL repair. DOG-1 was previously implicated in poly(G)/poly(C) (G/C) tract maintenance during DNA replication. G/C tracts remain stable in the absence of ATL-1, CLK-2 (FA pathway activators), FCD-2, BRC-2, and MLH-1 (associated FA components), implying that DOG-1 is the sole FA component required for G/C tract maintenance in a wild-type background. However, FCD-2 is required to promote deletion-free repair at G/C tracts in dog-1 mutants, consistent with a role for FA factors at the replication fork. The functional conservation between DOG-1 and FANCJ suggests a possible role for FANCJ in G/C tract maintenance in human cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Basic-Leucine Zipper Transcription Factors / physiology*
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Cross-Linking Reagents / pharmacology
  • DNA Helicases / chemistry
  • DNA Helicases / genetics
  • DNA Helicases / physiology*
  • DNA Repair / drug effects
  • DNA Repair / genetics
  • DNA Repair / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Fanconi Anemia Complementation Group Proteins / genetics
  • Fanconi Anemia Complementation Group Proteins / metabolism
  • Fanconi Anemia Complementation Group Proteins / physiology*
  • Immunohistochemistry
  • Molecular Sequence Data
  • Mutation
  • RNA Helicases / genetics
  • RNA Helicases / metabolism
  • RNA Helicases / physiology*
  • Sequence Homology, Amino Acid


  • BACH1 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • Caenorhabditis elegans Proteins
  • Cross-Linking Reagents
  • DNA-Binding Proteins
  • Fanconi Anemia Complementation Group Proteins
  • DNA Helicases
  • Dog-1 protein, C elegans
  • BRIP1 protein, human
  • RNA Helicases