Harrison L, Ascione G, Menninger J C, Ward D C, Demple B
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, MA 02115.
Hum Mol Genet. 1992 Dec;1(9):677-80. doi: 10.1093/hmg/1.9.677.
Abasic (AP) sites in DNA are produced spontaneously and by many genotoxic agents. The repair of such damages is initiated by AP endonucleases, which are evidently ubiquitous. We employed the recently cloned cDNA, APE, that encodes the major human AP endonuclease, to isolate large genomic fragments that contain the intact APE gene. The sequence of 3 kb encompassing APE was determined (GenBank Accession No. M99703). The APE gene contains four small introns (ranging 130 to 566 bp) and five exons, the first of which is untranslated. The 0.5 kb of DNA sequence upstream of APE did revealed only a possible CCAAT box, but no other regulatory sites or a TATA box, consistent with the constitutive expression of AP endonuclease activity observed in other studies. The location of APE in the human genome was mapped to chromosome 14, bands q11.2-12, by fluorescence in situ hybridization of metaphase cells with DNA from the genomic clones and subclones. Although this locus has not been associated causally with genetic diseases of DNA repair, some translocations that affect 14q11.2-12 could compromise APE and lead to genetic instability.
DNA中的无碱基（AP）位点可自发产生，也可由多种基因毒性剂诱导产生。此类损伤的修复由AP核酸内切酶启动，这些酶显然广泛存在。我们利用最近克隆的编码主要人类AP核酸内切酶的cDNA（APE），分离出包含完整APE基因的大片段基因组。测定了包含APE的3 kb序列（GenBank登录号M99703）。APE基因包含四个小内含子（长度在130至566 bp之间）和五个外显子，其中第一个外显子是未翻译的。APE上游0.5 kb的DNA序列仅显示出一个可能的CCAAT框，但没有其他调控位点或TATA框，这与其他研究中观察到的AP核酸内切酶活性的组成型表达一致。通过中期细胞与基因组克隆和亚克隆的DNA进行荧光原位杂交，将APE在人类基因组中的位置定位到14号染色体，q11.2 - 12带。尽管该位点尚未与DNA修复的遗传疾病有因果关联，但一些影响14q11.2 - 12的易位可能会损害APE并导致遗传不稳定。
