The atm-1 gene is required for genome stability in Caenorhabditis elegans.
The atm-1 gene is required for genome stability in Caenorhabditis elegans.
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DOI：
10.1007/s00438-012-0681-0
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Rose AM
中科院分区：
文献类型：
--
作者：
Jones MR;Huang JC;Chua SY;Baillie DL;Rose AM
人类共济失调-毛细血管扩张症-突变(ATM)基因被认为是一种罕见的常染色体疾病的基础，导致癌症易感性，现在被认为是响应DNA损伤的重要信号转导。秀丽线虫模型系统为理解该基因的保守功能提供了一种途径。本文描述了同源基因ATM-1的结构和功能缺失表型。利用生物信息学和分子分析，我们发现ATM-1基因先前被错误注释。我们发现，该转录本实际上是三个基因预测的产物，Y48G1B2(ATM-1)、K10E9.1和F56C11.4，它们共同构成了ATM-1的完整编码区。我们还描述了两个可用的敲除等位基因gk186和tm5027突变的动物的特征。正如预期的那样，ATM-1突变动物对电离辐射敏感。然而，此外，ATM-1突变体也表现出与基因组不稳定相关的表型，包括低孵化大小、活力降低和不育。我们记录了来自ATM-1突变动物的几种染色体融合。这是首次在线虫中描述ATM-1的突变子表型。最后，我们演示了如何使用平衡器系统来筛选和捕获ATM-1衍生的突变事件。我们的研究建立了线虫作为研究ATM突变子的模型，这可能导致开发筛选以识别人类的治疗靶点。本文的在线版本(doi：10.1007/s00438-012681-0)包含补充材料，授权用户可以使用。
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. The online version of this article (doi:10.1007/s00438-012-0681-0) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
Cheng, MY;Bullock, CM;Zhou, QY
通讯作者：
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作者：
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