Genome complexity: function of G-4 knots (Introduction)

by David Turell , Thursday, June 12, 2025, 20:45 (15 days ago) @ David Turell

Turn genes on and off:

https://phys.org/news/2025-06-unraveling-g4-cells-untie-dna.html

"Not all DNA looks like the familiar twisted ladder. Sometimes, parts of our genetic code fold into unusual shapes. One such structure, the G-quadruplex (G4), looks like a knot. These knots can play important roles in turning genes on or off. But if not untangled in time, they can harm our genome.

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"Human DNA is usually shaped like a double helix. However, under certain conditions, a single strand of DNA can fold into a G-quadruplex (G4) structure, which looks like a knot. These knots often form in regions with many guanine (G) bases. They help regulate important processes like transcription, where DNA is copied into RNA.

"But G4s are double-edged swords. While they help with gene regulation, if they are not untangled in time, they may cause mutations, disrupt gene expression, and even lead to cancer or early aging. Therefore, cells need tools to untie these knots quickly and efficiently.

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"...the researchers uncovered a surprising new role for RNA molecules. "With the help of proteins known for their role in DNA repair, RNA binds to the DNA strand opposite the G4 structure, forming a structure called a "G-loop." This G-loop structure is an important intermediate in the untangling mechanism and protects the genome from breaking down" says first author Koichi Sato.

"Although RNA is best known for its function in protein production through translation, this mechanism adds a previously unrecognized role for RNA in genome protection.

"The G-loop acts like a landing pad for additional proteins. These proteins untie the G4 knot, break apart the G-loop and convert the DNA to its normal double helix shape. Thanks to a collaboration with Simon Elsässer and Jing Lyu from the Karolinska Institute, the team discovered that the G-loop helps untie G4 knots across the entire genome.

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We were surprised to find that G4s are recognized as DNA lesions, even without real DNA damage," explains group leader Puck Knipscheer. The G-loop brings in proteins that usually fix DNA damage. But here, the cell treats the G4 structure as if it were broken DNA, triggering a DNA damage response. This allows the cell to act fast and prevent serious problems later.

"Even better, the process renews the surrounding DNA and removes harmful modifications.

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"...the team shows how important this mechanism is for cell health. When it fails, G4s build up and cause serious problems when the DNA needs to be copied before cell division. This results in DNA breaks and blocks cell growth.

Comment: a control and regulating process with repair all in one. If ever there was a clue pointing to design this is it.