Leonhardt E A, Kapp L N, Young B R, Murnane J P
Laboratory of Radiobiology and Environmental Health, University of California, San Francisco 94143-0750.
Genomics. 1994 Jan 1;19(1):130-6. doi: 10.1006/geno.1994.1022.
A radioresistant cell clone (1B3) was previously isolated after transfection of an ataxia-telangiectasia (AT) group D cell line with a human cosmid library. A cosmid rescued from the integration site in 1B3 contained human DNA from chromosome position 11q23, the same region shown by both genetic linkage and chromosome transfer to contain the genes for AT complementation groups A/B, C, and D. A gene within the cosmid (ATDC) was found to produce mRNAs of different sizes. A cDNA for one of the most abundant mRNAs (3.0 kb) was isolated from a HeLa cell library. In the present study, we sequenced the 3.0-kb cDNA and the surrounding intron DNA in the cosmids. We used polymerase chain reaction, with primers in the introns, to confirm the number of exons and to analyze DNA from AT group D cells for mutations within this gene. Although no mutations were found, we do not rule out the possibility that mutations may be present within the regulatory sequences or coding sequences found in other mRNAs specific for this gene. From the sequence analysis, we found that the ATDC gene product is one of a group of proteins that share multiple zinc finger motifs and an adjacent leucine zipper motif. These proteins have been proposed to form homo- or heterodimers involved in nucleic acid binding, consistent with the fact that many of these proteins appear to be transcriptional regulatory factors involved in carcinogenesis and/or differentiation. The likelihood that the ATDC gene product is involved in transcriptional regulation could explain the pleiomorphic characteristics of AT, including abnormal cell cycle regulation.
先前通过用人黏粒文库转染共济失调毛细血管扩张症（AT）D组细胞系，分离得到了一个耐辐射细胞克隆（1B3）。从1B3整合位点拯救出的一个黏粒含有来自染色体11q23位置的人类DNA，遗传连锁分析和染色体转移均表明该区域含有AT互补组A/B、C和D的基因。发现黏粒中的一个基因（ATDC）可产生不同大小的mRNA。从HeLa细胞文库中分离出了其中一种丰度最高的mRNA（3.0 kb）的cDNA。在本研究中，我们对3.0 kb cDNA以及黏粒中其周围的内含子DNA进行了测序。我们使用聚合酶链反应，以内含子中的引物来确认外显子数量，并分析AT D组细胞的该基因内的DNA是否存在突变。尽管未发现突变，但我们不排除在该基因其他特异性mRNA的调控序列或编码序列中可能存在突变的可能性。通过序列分析，我们发现ATDC基因产物是一组共享多个锌指基序和一个相邻亮氨酸拉链基序的蛋白质之一。这些蛋白质被认为可形成参与核酸结合的同二聚体或异二聚体，这与许多此类蛋白质似乎是参与致癌作用和/或分化的转录调节因子这一事实相符。ATDC基因产物参与转录调控的可能性可以解释AT的多形性特征，包括异常的细胞周期调控。
