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

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 pro...

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Main Authors:	Jones, Martin R., Huang, Jim Chin, Chua, Shu Yi, Baillie, David L., Rose, Ann M.
Format:	Online
Language:	English
Published:	Springer-Verlag 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313021/

id	pubmed-3313021
recordtype	oai_dc
spelling	pubmed-33130212012-03-30 The atm-1 gene is required for genome stability in Caenorhabditis elegans Jones, Martin R. Huang, Jim Chin Chua, Shu Yi Baillie, David L. Rose, Ann M. Original Paper 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. Springer-Verlag 2012-02-18 2012-04 /pmc/articles/PMC3313021/ /pubmed/22350747 http://dx.doi.org/10.1007/s00438-012-0681-0 Text en © The Author(s) 2012
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Jones, Martin R. Huang, Jim Chin Chua, Shu Yi Baillie, David L. Rose, Ann M.
spellingShingle	Jones, Martin R. Huang, Jim Chin Chua, Shu Yi Baillie, David L. Rose, Ann M. The atm-1 gene is required for genome stability in Caenorhabditis elegans
author_facet	Jones, Martin R. Huang, Jim Chin Chua, Shu Yi Baillie, David L. Rose, Ann M.
author_sort	Jones, Martin R.
title	The atm-1 gene is required for genome stability in Caenorhabditis elegans
title_short	The atm-1 gene is required for genome stability in Caenorhabditis elegans
title_full	The atm-1 gene is required for genome stability in Caenorhabditis elegans
title_fullStr	The atm-1 gene is required for genome stability in Caenorhabditis elegans
title_full_unstemmed	The atm-1 gene is required for genome stability in Caenorhabditis elegans
title_sort	atm-1 gene is required for genome stability in caenorhabditis elegans
description	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.
publisher	Springer-Verlag
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313021/
_version_	1611516840328036352

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

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