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arXiv 2109.12947cond-mat.softq-bio.BMq-bio.SC
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DNA复制极小模型中伸长的精度和速度

Accuracy and speed of elongation in a minimal model of DNA replication

M Sahoo, Arsha N, P R Baral, S Klumpp

摘要:

作为一种双重用途的酶,DNA聚合酶负责新形成的DNA链的延伸以及在错误掺入的情况下切割错误的生长。复制的效率取决于DNA聚合酶的聚合和核酸外切酶活性的协调。在这里,我们提出并分析了一个最小的DNA复制动力学模型,并确定了精确的表达式的延伸速度和复制的准确性。我们首先分析没有核酸外切酶活性的情况。在这种情况下,准确性是由步进和解结合之间的动力学竞争决定的,在两个转换中正确和不正确的核苷酸之间存在区别。然后,我们包括外切核酸酶活性,并询问外切核酸酶途径中的不同模式的额外区分如何提高准确性,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度。分析还表明,复制系统的设计并不普遍必须遵循的速度-精度权衡规则,虽然它在生物学实现的参数范围。该过程的准确性主要由错误掺入后的步进的关键作用控制,其对DNA聚合酶的聚合酶和核酸外切酶活性都有影响。

英文摘要:

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 exonuclase 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.

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