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Accuracy and speed of elongation in a minimal model of DNA replication
Physical Review E ( IF 2.2 ) Pub Date : 2021-09-28 , DOI: 10.1103/physreve.104.034417
M Sahoo 1, 2 , Arsha N 1 , P R Baral 2 , S Klumpp 3
Affiliation  

Being a dual purpose enzyme, the DNA polymerase is responsible for elongation of the newly formed DNA strand as well as cleaving the erroneous growth in case of a misincorporation. The efficiency of replication depends on the coordination of the polymerization and exonuclease activity of DNA polymerase. Here, we propose and analyze a minimal kinetic model of DNA replication and determine exact expressions for the velocity of elongation and the accuracy of replication. We first analyze the case without exonuclease activity. In that case, accuracy is determined by a kinetic competition between stepping and unbinding, with discrimination between correct and incorrect nucleotides in both transitions. We then include exonuclease activity and ask how different modes of additional discrimination in the exonuclease pathway can improve the accuracy while limiting the detrimental effect of exonuclease on the speed of replication. In this way, we ask how the kinetic parameters of the model have to be set to coordinate the two activities of the enzyme for high accuracy and high speed. The analysis also shows that the design of a replication system does not universally have to follow the speed-accuracy trade-off rule, although it does in the biologically realized parameter range. The accuracy of the process is mainly controlled by the crucial role of stepping after erroneous incorporation, which has impact on both polymerase and exonuclease activities of DNA polymerase.

中文翻译:

最小 DNA 复制模型中的延伸精度和速度

作为一种双重用途的酶,DNA 聚合酶负责延长新形成的 DNA 链,并在错误掺入的情况下切割错误的生长。复制效率取决于 DNA 聚合酶的聚合和核酸外切酶活性的协调。在这里,我们提出并分析了 DNA 复制的最小动力学模型,并确定了伸长速度和复制准确性的精确表达式。我们首先分析没有核酸外切酶活性的情况。在这种情况下,准确性由步进和解除绑定之间的动力学竞争决定,并区分两个转换中正确和不正确的核苷酸。然后我们包括外切核酸酶活性,并询问外切核酸酶途径中不同的额外区分模式如何提高准确性,同时限制外切核酸酶对复制速度的不利影响。通过这种方式,我们询问必须如何设置模型的动力学参数以协调酶的两种活性以实现高精度和高速。分析还表明,复制系统的设计并不普遍必须遵循速度 - 准确性权衡规则,尽管它在生物学实现的参数范围内确实如此。该过程的准确性主要由错误掺入后步进的关键作用控制,这对DNA聚合酶的聚合酶和核酸外切酶活性都有影响。通过这种方式,我们询问必须如何设置模型的动力学参数以协调酶的两种活性以实现高精度和高速。分析还表明,复制系统的设计并不普遍必须遵循速度 - 准确性权衡规则,尽管它在生物学实现的参数范围内确实如此。该过程的准确性主要由错误掺入后步进的关键作用控制,这对DNA聚合酶的聚合酶和核酸外切酶活性都有影响。通过这种方式,我们询问必须如何设置模型的动力学参数以协调酶的两种活性以实现高精度和高速。分析还表明,复制系统的设计并不普遍必须遵循速度 - 准确性权衡规则,尽管它在生物学实现的参数范围内确实如此。该过程的准确性主要由错误掺入后步进的关键作用控制,这对DNA聚合酶的聚合酶和核酸外切酶活性都有影响。尽管它在生物学实现的参数范围内。该过程的准确性主要由错误掺入后步进的关键作用控制,这对DNA聚合酶的聚合酶和核酸外切酶活性都有影响。尽管它在生物学实现的参数范围内。该过程的准确性主要由错误掺入后步进的关键作用控制,这对DNA聚合酶的聚合酶和核酸外切酶活性都有影响。
更新日期:2021-09-28
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