Moore P D, Rabkin S D, Osborn A L, Strauss B S
Biochimie. 1982 Aug-Sep;64(8-9):757-62. doi: 10.1016/s0300-9084(82)80125-9.
Adducts of 2-aminofluorene on the C-8 position of guanine block DNA synthesis and lead to mutation. N-acetylated adducts adopt the syn conformation such that in DNA the guanine is displaced from the helix by the fluorene ring while unacetylated adducts prefer the anti conformation allowing normal base pairing of the guanine with cytosine. In vitro synthesis by both E. coli DNA polymerase I and T4 DNA polymerase terminates predominantly one nucleotide before acetylated adducts but has an increased tendency to terminate opposite the unacetylated adducts apparently reflecting the preferred conformations of the two species of reacted nucleoside. In complete contrast AMV reverse transcriptase correctly inserts cytosine opposite the acetylated adducts but prefers to terminate one nucleotide before the unacetylated adducts. We interpret these results as indicating that the specific properties of a replicating polymerase can influence the conformation of a reacted nucleoside thus altering its recognition and possibly its mutagenic activity.
2-氨基芴在鸟嘌呤C-8位上形成的加合物会阻碍DNA合成并导致突变。N-乙酰化加合物采取顺式构象，因此在DNA中，芴环会将鸟嘌呤从螺旋中置换出来，而未乙酰化的加合物则更倾向于反式构象，从而使鸟嘌呤与胞嘧啶能够正常碱基配对。大肠杆菌DNA聚合酶I和T4 DNA聚合酶的体外合成主要在乙酰化加合物前一个核苷酸处终止，但在未乙酰化加合物相对位置处终止的倾向增加，这显然反映了两种反应性核苷的优先构象。完全相反的是，禽成髓细胞瘤病毒逆转录酶能正确地在乙酰化加合物相对位置处插入胞嘧啶，但在未乙酰化加合物前一个核苷酸处更倾向于终止。我们将这些结果解释为表明复制性聚合酶的特定性质可影响反应性核苷的构象，从而改变其识别能力并可能改变其诱变活性。
