Spectrum of mutational events in the absence of DOG-1/FANCJ in Caenorhabditis elegans

DNA Repair
Yang ZhaoAnn Rose

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.

References

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Citations

Dec 23, 2008·Cellular and Molecular Life Sciences : CMLS·Y WuR M Brosh
Feb 24, 2010·Nature Reviews. Molecular Cell Biology·Mary Ellen Moynahan, Maria Jasin
Nov 4, 2008·The Journal of Biological Chemistry·Timothy B C LondonKevin Hiom
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Feb 19, 2010·The Cancer Journal·Conleth G Murphy, Mary Ellen Moynahan
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Sep 5, 2009·Critical Reviews in Biochemistry and Molecular Biology·Kerstin Gari, Angelos Constantinou
Jul 20, 2010·FEBS Letters·Katrin PaeschkeVirginia A Zakian
Jul 11, 2009·Trends in Cell Biology·Hans J Lipps, Daniela Rhodes
Dec 9, 2008·Mutation Research·Jillian L YoudsSimon J Boulton
Feb 4, 2010·DNA Repair·Kevin Hiom
May 6, 2015·Trends in Genetics : TIG·Romulo SegoviaPeter C Stirling
Aug 1, 2010·Biomolecular Concepts·Sebastian L B KönigJulian L Huppert
Jul 2, 2011·Developmental Biology·Eliana VergheseBruce Wightman
Aug 22, 2012·G3 : Genes - Genomes - Genetics·Maja Tarailo-Graovac, Nansheng Chen

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