Replication of DNA is essential for cell division and the propagation of genetic information. The process is complex and involves multiple proteins working together to unwind and separate the two strands of the DNA double helix.
New cryo-electron microscopy (cryo-EM) images of an enzyme called helicase provide the most detailed view yet of how this separation occurs. The images, published in the journal *Nature*, reveal how helicase uses its "motor" domain to walk along the DNA molecule, while its "unwinding" domain separates the two strands.
This new understanding of the molecular mechanisms of helicase could lead to the development of new drugs that target this enzyme. Such drugs could help to inhibit the growth of cancer cells, which rely on rapid DNA replication to proliferate.
How helicase separates the DNA double helix
Helicase is a protein that plays a key role in the replication of DNA. It unwinds the double helix by breaking the hydrogen bonds between the base pairs and separating the two strands.
The cryo-EM images show helicase in action, with its motor domain wrapped around the DNA molecule and its unwinding domain extending out like a hand. The motor domain uses the energy from ATP hydrolysis to move along the DNA, while the unwinding domain separates the two strands.
The images also reveal that helicase interacts with a protein called single-stranded DNA-binding protein (SSB). SSB helps to stabilize the separated DNA strands and prevent them from reannealing.
Implications for cancer therapy
The new understanding of the molecular mechanisms of helicase could lead to the development of new drugs that target this enzyme. Such drugs could help to inhibit the growth of cancer cells, which rely on rapid DNA replication to proliferate.
One potential target for drugs is the interaction between helicase and SSB. By disrupting this interaction, it may be possible to inhibit helicase activity and prevent the separation of the DNA strands. This could lead to the death of cancer cells.
Cryo-EM is a powerful new technique that is providing insights into the molecular mechanisms of many important biological processes. The images of helicase in action are a beautiful example of this power and the potential for cryo-EM to lead to the development of new drugs.
