A possible mechanism for the dynamics of transition between polymerase and exonuclease sites in a high-fidelity DNA polymerase.
The fidelity of DNA synthesis by DNA polymerase is significantly increased by a mechanism of proofreading that is performed at the exonuclease active site separate from the polymerase active site. Thus, the transition of DNA between the two active sites is an important activity of DNA polymerase. Here, based on our proposed model, the rates of DNA transition between the two active sites are theoretically studied. With the relevant parameters, which are determined from the available crystal structure and other experimental data, the calculated transfer rate of correctly base-paired DNA from the polymerase to exonuclease sites and the transfer rate after incorporation of a mismatched base are in good agreement with the available experimental data. The transfer rates in the presence of two and three mismatched bases are also consistent with the previous experimental data. In addition, the calculated transfer rate from the exonuclease to polymerase sites has a large value even with the high binding affinity of 3'-5' ssDNA for the exonuclease site, which is also consistent with the available experimental value. Moreover, we also give some predictive results for the transfer rate of DNA containing only A:T base pairs and that of DNA containing only G:C base pairs.
Xie
Ping
P
Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100790, China. pxie@aphy.iphy.ac.cn
D000818:Animals; D020029:Base Pairing; D004247:DNA / Q000235:genetics; D004260:DNA Repair; D004261:DNA Replication / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D005092:Exonucleases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008957:Models, Genetic
D004247:DNA; D004259:DNA-Directed DNA Polymerase; D005092:Exonucleases