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Physics > Biological Physics
Title: ATP-dependent mismatch recognition in DNA replication mismatch repair
(Submitted on 7 Jun 2022 (v1), revised 15 Aug 2022 (this version, v2), latest version 30 Aug 2023 (v4))
Abstract: Mismatch repair (MMR) is one step of DNA replication after base selection and proofreading. It identifies mismatches and repairs them, increasing the fidelity of DNA replication by about 1000-fold. Such a good performance relies on its ability to recognize mismatches with high accuracy. However, there is a lack of studies on calculating the accuracy. The mismatch recognition mechanism has not been established. Most speculations are based on exploiting thermodynamic equilibrium and free energy. However, what is important may be non-equilibrium, maintained by consuming adenosine triphosphate (ATP). Here we explore this possibility. Since the knowledge of real MMR enzymes is incomplete, we use a hypothetical enzyme to study mismatch recognition that is ATP-dependent. We show that not only can the accuracy be calculated, but the replication fidelity can be reproduced. The hypothetical enzyme is a quantum system having three discrete energy levels corresponding to three different conformations. ATP raises the enzyme to the highest energy level to trigger a spontaneous quantum transition. The transition result is one of two low energy levels, each representing a different recognition result, i.e., a correct match or a mismatch. The transition probabilities are determined by the energy gap between the two low energy levels. The mechanism is that the energy gap flips to discriminate between mismatches and correct matches. We also calculate the rate of mistaking a correct match for a mismatch and incorporate the result into replication fidelity. The study of the hypothetical enzyme should shed light on the study of the real enzymes in MMR.
Submission history
From: Yong-Jun Zhang [view email][v1] Tue, 7 Jun 2022 05:58:30 GMT (742kb,D)
[v2] Mon, 15 Aug 2022 12:32:27 GMT (3467kb,D)
[v3] Fri, 2 Dec 2022 10:12:56 GMT (1798kb)
[v4] Wed, 30 Aug 2023 15:38:36 GMT (3470kb)
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