In a study published in the journal Science, researchers from various institutions reveal how DNA gyrase resolves DNA entanglements, providing insights into fundamental biological mechanisms with potential applications in biomedical treatment. While some DNA supercoiling is necessary for genetic reading and copying processes, too little or too much can be harmful. Understanding the role of DNA gyrase in untangling overwound DNA has been a mystery, but recent advancements in imaging techniques and the creation of supercoiled DNA loops have shed light on this process.
DNA minicircles were used to mimic the supercoiled and looped DNA structure found in living cells. Creating loops of supercoiled DNA allowed researchers to study the interactions between DNA gyrase and DNA minicircles using advanced imaging techniques like electron cryomicroscopy. This research provided a detailed understanding of how gyrase interacts with supercoiled loops of DNA to resolve entanglements, offering valuable insights into cellular processes that involve DNA supercoiling.
DNA supercoiling is essential for compacting linear DNA strands into the microscopic nucleus of a cell, allowing it to twist, fold, and form loops that regulate DNA activity. This study found that DNA gyrase is attracted to supercoiled minicircles and positions itself within the loop, cutting one DNA helix to pass the other through the break and reseal it. This mechanism relaxes overwinding and eases tangles, demonstrating how gyrase controls DNA supercoiling to regulate genetic activity.
The observations made in this study support the “DNA strand inversion model” proposed in 1979, providing experimental evidence for a hypothesis that has long been speculated but lacked confirmation. By using magnetic tweezers to examine the path of DNA wrapped around gyrase at a single-molecule level, researchers were able to uncover details that are often obscured in traditional experiments. This research opens up new avenues for studying the mechanisms of enzymes like gyrase, which have significant clinical value.
The findings of this study have broad implications for understanding how DNA activities are regulated and how supercoiling, looping, and 3-D shapes direct enzyme accessibility to specific DNA sequences. By studying the intricate interactions between enzymes like gyrase and DNA structures, researchers hope to gain insights that can impact cellular responses to antibiotics and other treatments. Overall, this research not only advances our understanding of fundamental biological mechanisms but also has practical implications for clinical treatments targeting bacterial infections and cancer.
