The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin
The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin
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DOI：
10.1038/ng1001-189
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发表时间：
2001-10-01
期刊：
影响因子：
30.8
通讯作者：
Koenig, M
中科院分区：
文献类型：
--
作者：
Moreira, MC;Barbot, C;Koenig, M
新发现的共济失调-眼用不能1（AOA 1; MIM 208920）（1-4）是日本常染色体隐性共济失调的最常见原因（2，4 -9），在葡萄牙仅次于Friedreich共济失调（10）。它与共济失调-毛细血管扩张症有几个共同的神经学特征，包括早发性共济失调、眼神经失用症和小脑萎缩，但没有共同的神经病学特征（免疫缺陷、染色体不稳定和对X射线超敏反应）。AOA 1的特征还在于轴突运动神经病（3，5，9）以及随后的血清白蛋白水平降低和总胆固醇升高（2，4，5，9）。我们已经确定了导致AOA 1的基因以及主要的葡萄牙和日本突变。这个基因编码一种新的，普遍表达的蛋白质，我们命名为aprataxin。该蛋白由三个结构域组成，分别与多核苷酸激酶3 '-磷酸酶（PNKP）的氨基末端结构域、组氨酸三联体（HIT）蛋白和DNA结合C2 H2锌指蛋白具有远端同源性。PNKP参与暴露于电离辐射和活性氧后的DNA单链断裂修复（SSBR）（11）。脆性HIT蛋白（FHIT）裂解二腺苷四磷酸，其可能在SSBR复合物活化期间产生（12）。结果表明，aprataxin是一种在DNA修复中起作用的核蛋白，这让人想起共济失调-毛细血管扩张症中蛋白质缺陷的功能，但当突变时会导致仅限于神经体征的表型。
The newly recognized ataxia-ocular apraxia 1 (AOA1; MIM 208920)(1-4) is the most frequent cause of autosomal recessive ataxia in Japan(2,4-9) and is second only to Friedreich ataxia in Portugal(10). It shares several neurological features with ataxia-telanglectasia, including early onset ataxia, oculomotor apraxia and cerebellar atrophy, but does not share its extraneurological features (immune deficiency, chromosomal instability and hypersensitivity to X-rays). AOA1 is also characterized by axonal motor neuropathy(3,5,9) and the later decrease of serum albumin levels and elevation of total cholesterol(2,4,5,9). We have identified the gene causing AOA1 and the major Portuguese and Japanese mutations. This gene encodes a new, ubiquitously expressed protein that we named aprataxin. This protein is composed of three domains that share distant homology with the amino-terminal domain of polynucleotide kinase 3'-phosphatase (PNKP), with histidine-triad (HIT) proteins and with DNA-binding C2H2 zinc-finger proteins, respectively. PNKP is involved in DNA single-strand break repair (SSBR)(11) following exposure to ionizing radiation and reactive oxygen species. Fragile-HIT proteins (FHIT) cleave diadenosine tetraphosphate, which is potentially produced during activation of the SSBR complex(12). The results suggest that aprataxin is a nuclear protein with a role in DNA repair reminiscent of the function of the protein defective in ataxia-telangiectasia, but that would cause a phenotype restricted to neurological signs when mutant.