Lieber M R
Dept of Pathology, Washington University School of Medicine, St Louis, MO 63110, USA.
Bioessays. 1997 Mar;19(3):233-40. doi: 10.1002/bies.950190309.
Unlike the most well-characterized prokaryotic polymerase, E. coli DNA pol l, none of the eukaryotic polymerases have their own 5' to 3' exonuclease domain for nick translation and Okazaki fragment processing. In eukaryotes, FEN-1 is an endo- and exonuclease that carries out this function independently of the polymerase molecules. Only seven nucleases have been cloned from multicellular eukaryotic cells. Among these, FEN-1 is intriguing because it has complex structural preferences; specifically, it cleaves at branched DNA structures. The cloning of FEN-1 permitted establishment of the first eukaryotic nuclease family, predicting that S. cerevisiae RAD2 (S. pombe Rad13) and its mammalian homolog, XPG, would have similar structural specificity. The FEN-1 nuclease family includes several similar enzymes encoded by bacteriophages. The crystal structures of two enzymes in the FEN-1 nuclease family have been solved and they provide a structural basis for the interesting steric requirements of FEN-1 substrates. Because of their unique structural specificities, FEN-1 and its family members have important roles in DNA replication, repair and, potentially, recombination. Recently, FEN-1 was found to specifically associate with PCNA, explaining some aspects of FEN-1 function during DNA replication and potentially in DNA repair.
与特征最明确的原核生物聚合酶大肠杆菌DNA聚合酶I不同，真核生物的聚合酶都没有用于切口平移和冈崎片段加工的自身5'至3'核酸外切酶结构域。在真核生物中，FEN-1是一种内切核酸酶和核酸外切酶，它独立于聚合酶分子执行此功能。从多细胞真核细胞中仅克隆出7种核酸酶。其中，FEN-1很有趣，因为它具有复杂的结构偏好；具体而言，它在分支DNA结构处切割。FEN-1的克隆使得第一个真核核酸酶家族得以建立，预测酿酒酵母RAD2（粟酒裂殖酵母Rad13）及其哺乳动物同源物XPG具有相似的结构特异性。FEN-1核酸酶家族包括由噬菌体编码的几种相似的酶。FEN-1核酸酶家族中两种酶的晶体结构已得到解析，它们为FEN-1底物有趣的空间需求提供了结构基础。由于其独特的结构特异性，FEN-1及其家族成员在DNA复制、修复以及潜在的重组中具有重要作用。最近，发现FEN-1与增殖细胞核抗原（PCNA）特异性结合，这解释了FEN-1在DNA复制期间以及可能在DNA修复中的某些功能方面。
