title: Spectrum of mutational events in the absence of DOG-1/FANCJ in Caenorhabditis elegans.
abstract: The Caenorhabditis elegans ortholog of the Fanconi anemia pathway component J (FANCJ) is DOG-1, which is essential for genome stability. Previous studies have shown that disruption of the dog-1 gene generates small deletions of poly-C/poly-G tracts detectable by PCR and results in a mutator phenotype. In this paper, we describe the isolation and characterization of lethal mutations resulting from the loss of dog-1 function. The mutant strains were analyzed using a combination of techniques including genetic mapping, SNP mapping, and oaCGH (oligo array Comparative Genome Hybridization). Using the eT1 balancer system to recover lethal mutants, we isolated, in addition to small deletions, large chromosomal rearrangements, including duplications, translocations and deficiencies. The forward mutation frequency was 10-fold higher than the spontaneous frequency for eT1, and equivalent to that observed for low doses of standard mutagens. From a screen for suppressors of mdf-1/MAD1 lethality, we previously had isolated such-4(h2168), shown here to be a large tandem duplication. Thus, the range of mutational events caused by lack of DOG-1/FANCJ is much broader than previously described.
authors: Department of Medical Genetics, University of British Columbia, 419-2125 East Mall, Vancouver, BC, Canada.
authors: Yang
authors: Y
authors: Zhao
authors: Maja
authors: M
authors: Tarailo-Graovac
authors: Nigel J
authors: NJ
authors: O'Neil
authors: Ann M
authors: AM
authors: Rose
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002874:Chromosome Mapping; D002875:Chromosomes / Q000648:ultrastructure; D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism*; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D005819:Genetic Markers; D008954:Models, Biological; D008957:Models, Genetic; D009153:Mutagens; D009154:Mutation; D009693:Nucleic Acid Hybridization; D020641:Polymorphism, Single Nucleotide
chemical_list: D029742:Caenorhabditis elegans Proteins; D005819:Genetic Markers; D009153:Mutagens; D004265:DNA Helicases; C464789:Dog-1 protein, C elegans