Science & Technology

Abnormal “quadruple helix” structure of DNA may be behind rare aging syndrome

The double helix structure is effectively synonymous with DNA, but it is not the only way long strands of genetic information can be pushed into tight spaces.

When a double strand of DNA doubles back to itself or attaches to another double strand, it can actually tie a quadruplex knot known as a G-quadruplex.

scientist First discovered These “double double helices” of living human cells in 2013, and since then these knots have been High concentration With cancer cells.

Researchers at Imperial College London now associate the accumulation of G-quadruplexes with another human illness-a rare hereditary disorder known as Cockayne syndrome (CS).

CS is a recessive disorder that affects multiple systems in the body. It is characterized by premature aging, sun sensitivity, cerebral atrophy, and failure to thrive.

Most often, this disorder is associated with a mutation in the Cockayne Syndrome B (CSB) protein, and in laboratory experiments involving human, insect, and bacterial cells, researchers said the protein was “Amazing picomolar affinity“To G-quadruplexes formed from multiple different DNA strands.

In contrast, these proteins do not appear to bind with approximately the same affinity for a double helix that simply reverts to a double helix to create a four-stranded structure.

This is an important discovery. It suggests that the CSB protein plays a role in mixing and matching DNA strands in the cell nucleus, especially for ribosomal DNA.

This type of DNA carries the transcriptional code of cellular proteins, so if the CSB proteins mutate and become unable to bind to the G-quadruplex, these proteins may not be produced.

Previous experiment The lack of functional CSB indicates that it tends to arrest transcription of the G-quadruplex structure. Without this messenger copy of DNA, genetic information cannot leave the cell and communicate with other parts of the body.

“Given that loss of CSB induces an early aging phenotype, our findings indicate that the interaction between CSB and ribosomal DNA intramolecular G4 is essential for maintaining cell homeostasis. “The authors state. explanation..

If the researchers are right and these findings apply to the body in real-life situations, Cockayne syndrome can lead to premature aging because it interferes with the production of the protein encoded by a particular G-quadruplex.

Most studies on G-quadruplexes so far have focused on the structure formed when a single double helix molecule folds back into itself. However, this new study is part of the first study investigating the role of G-quadruplexes formed from two separate double helix molecules.

“Our genomic DNA is more than 2 meters long, but is compressed into a space that is only a few microns in diameter. Therefore, there is a way to use long-range loop structures to compress DNA in a more complex way. That’s not surprising. Interactions beyond imagination. ” To tell Marco Di Antonio, a chemical biologist at Imperial College London.

“We don’t know much about DNA yet, but our results show that the way and location of G-quadruplex structures influences their function and is more biological than previously thought. Shows that it will be important. “

New research may ultimately help researchers come up with cures for diseases like Cockayne Syndrome. Perhaps this rare degenerative disease could be alleviated in the future if the dysfunctional CSB can be stopped from binding to G-quadruplexes in the first place.

The study was published in Journal of the American Chemical Society..

Abnormal “quadruple helix” structure of DNA may be behind rare aging syndrome Abnormal “quadruple helix” structure of DNA may be behind rare aging syndrome

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