Scientists at the University of Cambridge reported Sunday that they have discovered quadruple helix DNA inside human cells by creating synthetic molecules that seek it out — raising the potential that future medicines may be able to pinpoint and shut down DNA replication within cancerous tumors.
Although the findings, published in the scientific journal Nature Chemistry, still leave a lot of unanswered questions about quadruple helix DNA, the work released Sunday is a breakthrough brought about by more than a decade of research.
Still, 60 years on from the discovery of DNA, scientists do not know why traditionally double helix structures loop back in on themselves sometimes during replication. They’ve known these structures exist in a laboratory setting, but the Cambridge findings are the first to pinpoint the formation of “quadruplexes” within living human cells.
Observing the structures was no easy feat, however. Scientists had to create synthetic bio-luminescent antibody proteins that seek out and bind to quadruplexes at various stages in cell division. The proteins were built in such a way that they glow more brightly during DNA replication.
Using those markers, researchers noticed that the proteins are able to “trap” quadruplexes and stabilize their production, potentially opening up a new avenue for cancer treatments.
“We are seeing links between trapping the quadruplexes with molecules and the ability to stop cells dividing, which is hugely exciting,” Professor Shankar Balasubramanian said in an advisory.
“The research indicates that quadruplexes are more likely to occur in genes of cells that are rapidly dividing, such as cancer cells,” he added. “For us, it strongly supports a new paradigm to be investigated – using these four-stranded structures as targets for personalized treatments in the future.”
Balasubramanian also warned that so little is known about quadruplexes that interfering with their production may not ultimately prove helpful. “One thought is that these quadruplex structures might be a bit of a nuisance during DNA replication – like knots or tangles that form,” he said.
“Did they evolve for a function?” Balasubramanian added. “It’s a philosophical question as to whether they are there by design or not – but they exist and nature has to deal with them. Maybe by targeting them we are contributing to the disruption they cause.”
Though much work is left to be done, the group that funded the study, Cancer Research UK, believes it could lead to a revolution in cancer therapies.
“This research further highlights the potential for exploiting these unusual DNA structures to beat cancer – the next part of this pipeline is to figure out how to target them in tumor cells,” Dr. Julie Sharp at Cancer Research UK said in an advisory. “It’s been sixty years since its structure was solved but work like this shows us that the story of DNA continues to twist and turn.”
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