Imai T, Yamauchi M, Seki N, Sugawara T, Saito T, Matsuda Y, Ito H, Nagase T, Nomura N, Hori T
Genome Research Group, National Institute of Radiological Sciences, Chiba, Japan.
Genome Res. 1996 May;6(5):439-47. doi: 10.1101/gr.6.5.439.
Ataxia telangiectasia (AT) is an autosomal recessive disease of unknown etiology associated with cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, and hypersensitivity to ionizing radiation. Although AT has been divided into four complementation groups by its radioresistant-DNA synthesis phenotype, the ATM gene has been isolated as the candidate gene responsible for all AT groups. We identified a new gene, designated NPAT, from the major AT locus on human chromosome 11q22-q23. The gene encoded a 1421-amino-acid protein containing nuclear localization signals and phosphorylation target sites by cyclin-dependent protein kinases associated with E2F. The messenger RNA of NPAT was detected in all human tissues examined, and its genomic sequence was strongly conserved through eukaryotes, suggesting that the NPAT gene may be essential for cell maintenance and may be a member of the housekeeping genes. Analysis of the genomic region of NPAT surprisingly revealed that the gene existed only 0.5 kb apart from the 5' end of the ATM transcript with opposite transcriptional direction. It may be possible to propose the idea that the promoter region could be shared by both housekeeping genes and that each gene could influence the expression of the other.
共济失调毛细血管扩张症（AT）是一种病因不明的常染色体隐性疾病，与小脑共济失调、眼皮肤毛细血管扩张、免疫缺陷以及对电离辐射过敏有关。尽管AT根据其抗辐射DNA合成表型已被分为四个互补组，但ATM基因已被分离出来作为所有AT组的候选基因。我们从人类染色体11q22 - q23上的主要AT位点鉴定出一个新基因，命名为NPAT。该基因编码一个1421个氨基酸的蛋白质，含有核定位信号以及与E2F相关的细胞周期蛋白依赖性蛋白激酶的磷酸化靶位点。在所有检测的人体组织中都检测到了NPAT的信使RNA，并且其基因组序列在真核生物中高度保守，这表明NPAT基因可能对细胞维持至关重要，可能是管家基因的一员。对NPAT基因组区域的分析令人惊讶地发现，该基因与ATM转录本的5'端仅相距0.5 kb，且转录方向相反。有可能提出这样的观点，即启动子区域可能由两个管家基因共享，并可能相互影响彼此的表达。
