Specific mismatch recognition in heteroduplex intermediates by p53 suggests a role in fidelity control of homologous recombination
Specific mismatch recognition in heteroduplex intermediates by p53 suggests a role in fidelity control of homologous recombination
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DOI：
10.1128/mcb.18.9.5332
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发表时间：
1998-09-01
影响因子：
5.3
通讯作者：
Wiesmüller, L
中科院分区：
文献类型：
--
作者：
Dudenhöffer, C;Rohaly, G;Wiesmüller, L
我们证明，野生型p53抑制同源重组。为了分析在这个过程中的DNA底物特异性，我们设计了重组实验，使猴病毒40突变体对的共感染产生异源双链体，具有明显的未配对区域。产生单个C-T和A-G错配的DNA交换比产生G-T和A-C单碱基错配或包含G-T/A-C错配的三个碱基对的未配对区域的DNA交换更有效地抑制四到六倍。p53特异性结合三链DNA底物，模拟早期重组中间体。p53与显示不同配对和未配对区域的三链底物相互作用的K-D值反映了在重组测定中以定性和定量方式观察到的错配碱基特异性。在这些结果的基础上，我们想提出这样的假设，即p53，像经典的错配修复因子，检查特异性错配识别的同源重组过程的保真度。
We demonstrate that wild-type p53 inhibits homologous recombination. To analyze DNA substrate specificities in this process, we designed recombination experiments such that coinfection of simian virus 40 mutant pairs generated heteroduplexes with distinctly unpaired regions. DNA exchanges producing single C-T and A-G mismatches were inhibited four- to sixfold more effectively than DNA exchanges producing G-T and A-C single-base mispairings or unpaired regions of three base pairs comprising G-T/A-C mismatches. p53 bound specifically to three-stranded DNA substrates, mimicking early recombination intermediates. The K-D values for the interactions of p53 with three-stranded substrates displaying differently paired and unpaired regions reflected the mismatch base specificities observed in recombination assays in a qualitative and quantitative manner. On the basis of these results, we would like to advance the hypothesis that p53, like classical mismatch repair factors, checks the fidelity of homologous recombination processes by specific mismatch recognition.