Watanabe S M, Goodman M F
Proc Natl Acad Sci U S A. 1981 May;78(5):2864-8. doi: 10.1073/pnas.78.5.2864.
We address the question of whether substituting 2-aminopurine (APur) in place of adenine (Ade) in DNA can increase the frequency of base mispairing with cytosine. Using DNA polymerase alpha to measure the rates of inserting deoxycytidine and thymidine nucleotides in direct competition with each other for APur or Ade sites on synthetic copolymer DNA templates, we observe that the ratio of dCMP to dTMP insertion is increased by a factor of at least 230 when APur replaces Ade on a poly(dA) template and by a factor of 35 when APur replaces Ade on a poly(dC,dA) template. These data support the idea that APur.C base mispairs are directly involved in APur induction of A.T leads to G.C transition mutations. The observed misinsertion frequency of cytosine substituting for thymine opposite template APur sites is about 5%. This value is in excellent agreement with earlier predictions and measurements for APur.C heteroduplex-heterozygote frequencies in T4 bacteriophage in vivo.
我们探讨了在DNA中用2-氨基嘌呤（APur）取代腺嘌呤（Ade）是否会增加与胞嘧啶碱基错配频率的问题。利用DNA聚合酶α来测量在合成共聚物DNA模板上脱氧胞苷和胸苷核苷酸相互直接竞争APur或Ade位点时的插入速率，我们观察到当在聚（dA）模板上APur取代Ade时，dCMP与dTMP插入的比率增加了至少230倍，而当在聚（dC，dA）模板上APur取代Ade时，该比率增加了35倍。这些数据支持了APur·C碱基错配直接参与APur诱导A·T导致G·C转换突变的观点。观察到在模板APur位点对面胞嘧啶取代胸腺嘧啶的错误插入频率约为5%。该值与早期对T4噬菌体体内APur·C异源双链体-杂合子频率的预测和测量结果非常吻合。
