Researchers at the Francis Crick Institute have uncovered how the double helix structure of DNA is opened to allow DNA replication. The work could lead to further studies to better understand this process, including how it can go wrong in diseases such as cancer.
Since the discovery of the double helix structure of DNA nearly 70 years ago, scientists have worked to understand how the two strands of DNA are opened to access genetic information. This opening is essential for processes including DNA repair, gene expression, and replication of DNA for cell division.
In their study published in Nature Today (June 15), scientists collaborated with Crick’s Chromosome Replication Laboratory to use a yeast model to better understand how the enzyme that opens DNA for replication works. The scientists used an advanced imaging method called cryo-electron microscopy to visualize the entire process of the DNA double helix without twisting and unwinding.
The team observed that, after engulfing the DNA, the two enzymes move away from each other in a process that distorts the double helix, triggering the process of DNA unwinding.
Alessandro Costa, author and group leader at the Macromolecular Machines Laboratory at Crick, says: “For decades, scientists, including our colleague John Defley at Crick, have pieced together which enzymes are needed to open DNA and initiate replication.
“We now looked at replication initiation under the microscope and found that the mechanism is completely different from the way the DNA double helix opens to initiate other cellular processes, such as gene transcription and recombination. We hope to understand this difference.” will allow us and other research groups to build a comprehensive picture that captures the complexities of life.”
Jacob Lewis, author and postdoctoral training fellow in the Macromolecular Machines Laboratory at Crick, says: “Understanding the mechanism of melting of the DNA double helix provides the basis for studying how the initiation of DNA replication is controlled. Important for understanding this The effect is the maintenance of chromosomal integrity, a process that goes wrong in cancer.”
Scientists will continue this work to understand how the DNA replication machinery opens the double helix after it is opened and how it is regulated to avoid the accumulation of DNA damage.
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Jacob S. Lewis et al, Mechanism of nucleated replication origin melting by CMG helicase assembly, Nature (2022). DOI: 10.1038/s41586-022-04829-4
Provided by Francis Crick Institute
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