Today, for the first time, researchers have directly witnessed the first motion of unwinding DNA, a fundamental process on which all living things rest. This breakthrough brings a better understanding of the processes through which cells duplicate genetic information, an aspect of growth and reproduction.
At King Abdullah University of Science and Technology (KAUST), the pictures taken through cryo-electron microscopy and deep learning throw light on the interaction between the helicase enzyme, particularly that of Simian Virus 40 Large Tumor Antigen (LTag), and DNA. Out of the 15 distinct atomic states through which helicase has been shown to initiate the separation of the DNA double helix, they have also been identified.
Helicases are pivotal enzymes that unwind the double-stranded DNA, enabling replication to take place. Prior to this study, the precise mechanics of helicases, DNA, and adenosine triphosphate (ATP) working together to drive this unwinding were not fully understood. The research results showed that ATP hydrolysis-the breakdown of ATP molecules-causes conformational changes in helicases. These results eventually destabilize and separate the DNA strands like a spring mechanism that drives the helicase along the DNA.
Another interesting finding was that two helicase molecules can coordinate their activity to shuttle helices in opposite directions around the DNA by binding simultaneously to independent sites on the same DNA strand. This cooperation is energy efficient, as one would expect from nanomachines of nature. Such a mechanism not only informs the answers to some very basic conceptual issues in DNA replication, but also yields insights for potential engineering of nanomachines.
The current study is a major development in molecular biology, involving morphing DNA replication into a much clearer picture. Further, these findings may also be useful for applications in bringing about new nanotechnologies and therapy approaches to genetic diseases.
Research shows how helicases keep genetic integrity and point new horizons toward further studies into energy-efficient mechanisms of molecular machines. By helping to define initial stages of DNA unwinding, it will further advance understanding of the complexity of cellular processes against technological advancements inspired by these biological systems.
