Untangle DNA
Physicist Julia Bakx obtained new insights into how cells resolve knots and twists in DNA using advanced optical tweezers. That process is essential for healthy cell division, DNA repair and preventing errors in the hereditary material. She focused on the human protein complex Topoisomerase IIIα along with its auxiliary proteins RMI1 and RMI2, collectively known as TRR.
During processes such as DNA replication, DNA frequently gets tangled. To prevent damage and errors, these structures must be accurately resolved. The study showed that TRR can cut single-stranded DNA, creating an opening of about 8.3 nanometers. Interestingly, the protein complex was found to be able to untangle not only knots in single-stranded DNA, but also structures containing double-stranded DNA. This result was unexpected and offers new insights into the flexibility of the protein mechanism.
In addition, Bakx discovered that the process can also be reversed: TRR turns out to be able to twist two strands of DNA precisely around each other to form new knots. This provides a more complete picture of how these proteins can actively modify the structure of DNA.
In addition to the biological discoveries, Bakx also developed a new experimental method using four optical tweezers. With these, two strands of DNA could be twisted around each other several times without having to attach the DNA to a surface. In previous experiments, such an attachment was always necessary. The new approach makes it possible to study DNA-protein interactions more faithfully and accurately, especially for complex DNA structures.
The results contribute to a better understanding of fundamental processes such as DNA replication and DNA repair. This is socially relevant because errors in these processes can lead to genetic disorders and diseases such as cancer. Moreover, the new method can help researchers in the future to more specifically investigate how proteins protect and repair DNA, which may ultimately contribute to the development of new medical treatments.
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