Enzymes hold the answer to understanding how DNA mutates

According to recent research from the University of Surrey, enzymes, which are essential for regulating how cells replicate in the human body, could be the very component that encourages DNA to spontaneously mutate, leading to potentially permanent genetic errors.

Enzymes hold the answer to understanding how DNA mutates

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Researchers from Surrey’s Quantum Biology Doctoral Training Centre discovered that the portion of the process by which DNA replicates itself happens at speeds 100 times more rapidly than previously predicted using advanced quantum chemical calculations.

The presumption that quantum effects would not endure long enough to be affected by the replication process is clarified by this finding.

We always thought that quantum mechanics would suffer in a biological environment. However, it was fascinating to find that the mutations caused by quantum tunelling are more stable due to the action of the enzyme, helicase. While others have painted helicase as a gatekeeper to quantum mutation, our research suggests that the enzyme is deeply intertwined with the formation of these mutations.

Max Winokan, Study Co-Author and Postgraduate Research Student, University of Surrey

The pairing rules between the genetic letters on opposing strands and DNA’s remarkable stability are both a result of this well-known double helix structure. Due to the different structures of these biomolecules and the various numbers of hydrogen bonds formed between these base pairs, A typically always binds to T, while G always binds to C.

Occasionally, the protons (hydrogen atom nuclei) forming these bonds move across them to create the uncommon states known as tautomers.

DNA replication, which is required for a cell to start replicating itself, starts with the two DNA strands being divided so that each can serve as a template for new DNA. An enzyme known as a “helicase,” which binds to one of the DNA strands and pulls it through itself to force the DNA apart, is what makes it possible for the strands to separate.

To have a chance of resulting in irreversible genetic errors, potential mutant DNA bases must endure this process.

Prior to now, it was believed that the helicase action was too slow. Since the strands are separated, any unintentional point mutation would have found its way back to its natural and more stable position.

The latest findings begin to explain how quantum mechanical phenomena might hold the key to understanding genetic mutations and the numerous negative effects they have on Earth’s ecosystem. This new study also discovers that such a mechanical separation stabilizes DNA mutations.

There is little understanding of the role of quantum effects in DNA damage and genetic mutations. We believe that we can shed light on the elusive mechanism at the origin of DNA errors only by integrating quantum physics and computational chemistry.

Dr Marco Sacchi, Study Lead, Royal and Society University Research Fellow, Computational Surface Science and Materials Modelling, University of Surrey

Professor Jim Al-Khalili, co-director of the Quantum Biology Doctoral Training Centre at the University of Surrey, stated, “What I find most exciting is that this work brings together cutting-edge research across disciplines: physics, chemistry and biology, to answer one of the most intriguing questions in science today, and the University of Surrey is fast becoming a world leader in this field where exciting results are emerging.

Source:
Journal reference:

Slocombe, L., et al. (2022). Proton transfer during DNA strand separation as a source of mutagenic guanine-cytosine tautomers. Nature. doi.org/10.1038/s42004-022-00760-x

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