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Disruption of dog-1 in Caenorhabditis elegans triggers deletions upstream of guanine-rich DNA

Nature Genetics volume 31, pages 405–409 (2002)Cite this article

Abstract

Genetic integrity is crucial to normal cell function, and mutations in genes required for DNA replication and repair underlie various forms of genetic instability and disease, including cancer1. One structural feature of intact genomes is runs of homopolymeric dC/dG. Here we describe an unusual mutator phenotype in Caenorhabditis elegans characterized by deletions that start around the 3′ end of polyguanine tracts and terminate at variable positions 5′ from such tracts. We observed deletions throughout genomic DNA in about half of polyguanine tracts examined, especially those containing 22 or more consecutive guanine nucleotides. The mutator phenotype results from disruption of the predicted gene F33H2.1, which encodes a protein with characteristics of a DEAH helicase and which we have named dog-1 (for deletions of guanine-rich DNA). Nematodes mutated in dog-1 showed germline as well as somatic deletions in genes containing polyguanine tracts, such as vab-1. We propose that DOG-1 is required to resolve the secondary structures of guanine-rich DNA that occasionally form during lagging-strand DNA synthesis.

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Figure 1: Mutation of dog-1 results in a mutator phenotype.
Figure 2: Recurrent deletions in the gk10 strain invariably start at tracts of C/G.
Figure 3: Disruption of DOG-1 expression leads to frequent deletions involving the polyguanine tract in F55F3.
Figure 4: Model of recurrent deletions in gk10 nematodes.

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Acknowledgements

This paper is dedicated to the memory of M. Smith, who died in October 2000. We thank D. Baillie for discussion and help with the analysis, R. Kay for critical reading of the manuscript and V. Vijayaratnam for outcrossing the gk10 strain. This work was supported by a grant from the National Cancer Institute of Canada with funds from the Terry Fox Run and by grants from the Canadian Institute of Health Research (A.R. and P.L.). I.C. was supported by a studentship from the University of British Columbia.

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Authors and Affiliations

  1. Terry Fox Laboratory, British Columbia Cancer Agency, 10th Avenue, Vancouver, V5Z 1L3, British Columbia, Canada

    Iris Cheung, Michael Schertzer & Peter M. Lansdorp

  2. Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada

    Iris Cheung & Ann Rose

  3. Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

    Peter M. Lansdorp

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Correspondence to Peter M. Lansdorp.

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Cheung, I., Schertzer, M., Rose, A. et al. Disruption of dog-1 in Caenorhabditis elegans triggers deletions upstream of guanine-rich DNA. Nat Genet 31, 405–409 (2002). https://doi.org/10.1038/ng928

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