Second human protein with homology to the Escherichia coli abasic endonuclease exonuclease III
Second human protein with homology to the Escherichia coli abasic endonuclease exonuclease III
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DOI：
10.1002/1098-2280(2000)36:4
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发表时间：
2000-01-01
影响因子：
2.8
通讯作者：
Wilson, DM
中科院分区：
文献类型：
--
作者：
Hadi, MZ;Wilson, DM
有两个主要的脱嘌呤/脱嘧啶（AP）核酸内切酶/3 '-二酯酶家族，以大肠杆菌蛋白质核酸外切酶III（ExoIII）和核酸内切酶IV（EndoIV）命名。这些修复蛋白的功能是从DNA中切除诱变和细胞毒性AP位点或3 '-磷酸/磷酸乙醇酸基团。在哺乳动物中，主要的修复核酸内切酶是Ape 1，它是ExoIII的同源物，而哺乳动物中EndoIV的同源物迄今尚未鉴定。我们已经鉴定了一种名为Ape 2的人蛋白，其代表ExoIII家族的一个亚类（与酿酒酵母ETH 1/APN 2基因产物具有最高的相似性），并保留了ExoIII样蛋白的许多必需功能残基。人蛋白质为518个氨基酸，预测分子量为57.3 kDa，pi为8.65。与Ape 1不同，该蛋白仅表现出弱的能力来补充AP内切酶/3 '-修复缺陷型细菌和酵母的修复缺陷。类似地，用部分纯化的Ape 2蛋白观察到对含脱碱基位点的底物的弱但特异的DNA结合和切割活性。APE 2位于X染色体p11.21位置，由6个外显子组成。APE 2的转录本广泛表达，表明编码蛋白的重要功能。Ape 2绿色荧光融合蛋白主要定位于Hela细胞核，表明具有核功能;这种定位依赖于C-末端结构域。我们讨论了我们的研究结果的背景下，进化保守的AP核酸内切酶家族和他们的不同活动和生物学贡献。Environ.梅尔. h变异体36：312-324，2000.出版2000威利利斯，公司匕首
There are two major apurinic/apyrimidinic (AP) endonuclease/3'-diesterase families designated after the Escherichia coli proteins exonuclease III (ExoIII) and endonuclease IV (EndoIV). These repair proteins function to excise mutagenic and cytotoxic AP sites or 3'-phosphate/phosphoglycolate groups from DNA. In mammals, the predominant repair endonuclease is Ape1, a homolog of ExoIII, whereas a mammalian homolog to EndoIV has not been identified to date. We have identified a human protein termed Ape2 that represents a subclass of the ExoIII Family (exhibiting highest similarity to the Saccharomyces cerevisiae ETH1/APN2 gene product) and maintains many of the essential functional residues of the ExoIII-like proteins. The human protein is 518 amino acids with a predicted molecular mass of 57.3 kDa and a pi of 8.65. Unlike Ape1, this protein exhibited only weak ability to complement the repair defects of AP endonuclease/3'-repair-defective bacteria and yeast. Similarly, a weak, but specific, DNA-binding and incision activity for abasic site-containing substrates was observed with partially purified Ape2 protein. APE2 is located on the X chromosome at position p11.21 and consists of six exons. The transcript for APE2 is ubiquitously expressed, suggesting an important function for the encoded protein. An Ape2 green fluorescent fusion protein localized predominantly to the nucleus of Hela cells, indicating a nuclear Function; this localization was dependent on the C-terminal domain. We discuss our results in the context of the evolutionary conservation of the AP endonuclease families and their divergent activities and biological contributions. Environ. Mel. Mutagen. 36:312-324, 2000. Published 2000 Wiley Liss, Inc.dagger