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Mol Genet Genomics. 2012 Apr;287(4):325-35. doi: 10.1007/s00438-012-0681-0. Epub 2012 Feb 18.

The atm-1 gene is required for genome stability in Caenorhabditis elegans.

Author information

1
Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. mjones@gene.nce.ubc.ca

Abstract

The Ataxia-telangiectasia-mutated (ATM) gene in humans was identified as the basis of a rare autosomal disorder leading to cancer susceptibility and is now well known as an important signal transducer in response to DNA damage. An approach to understanding the conserved functions of this gene is provided by the model system, Caenorhabditis elegans. In this paper we describe the structure and loss of function phenotype of the ortholog atm-1. Using bioinformatic and molecular analysis we show that the atm-1 gene was previously misannotated. We find that the transcript is in fact a product of three gene predictions, Y48G1BL.2 (atm-1), K10E9.1, and F56C11.4 that together make up the complete coding region of ATM-1. We also characterize animals that are mutant for two available knockout alleles, gk186 and tm5027. As expected, atm-1 mutant animals are sensitive to ionizing radiation. In addition, however, atm-1 mutants also display phenotypes associated with genomic instability, including low brood size, reduced viability and sterility. We document several chromosomal fusions arising from atm-1 mutant animals. This is the first time a mutator phenotype has been described for atm-1 in C. elegans. Finally we demonstrate the use of a balancer system to screen for and capture atm-1-derived mutational events. Our study establishes C. elegans as a model for the study of ATM as a mutator potentially leading to the development of screens to identify therapeutic targets in humans.

PMID:
22350747
PMCID:
PMC3313021
DOI:
10.1007/s00438-012-0681-0
[Indexed for MEDLINE]
Free PMC Article

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