Biochemical controls of DNA repair (Introduction)

by David Turell , Saturday, June 07, 2025, 20:32 (4 days ago) @ David Turell

Go and stop proteins:

https://phys.org/news/2025-06-protein-droplets-shield-fragile-dna.html

"Now, scientists Irene Chiolo and Chiara Merigliano at the USC Dornsife College of Letters, Arts and Sciences have discovered that a protein called Nup98, long known for helping traffic molecules in and out of the cell's nucleus, plays another surprising role: guiding the cell's most delicate repairs and reducing the risk of genetic mistakes that can lead to cancer. Their findings were published in Molecular Cell.

"With support from the National Institutes of Health, the National Science Foundation, and the American Cancer Society, the researchers revealed that Nup98 forms droplet-like structures deep inside the nucleus. These "condensates" act as protective bubbles around broken strands of DNA in areas called heterochromatin—zones where the genetic material is so tightly packed that making accurate repairs is especially challenging.

"Heterochromatin—a major focus of Chiolo's research—is filled with repeated DNA sequences, making it easy for the cell to confuse one stretch for another. Nup98's droplets help lift the damaged section out of that dense zone and create a safer space where it can be repaired accurately, reducing the chance of genetic mix-ups that could lead to cancer.

"The researchers also found that Nup98 helps mobilize the damaged site in tightly packed heterochromatin, so it can reach a different part of the nucleus where repair is safer.

"Timing is everything when it comes to DNA repair, and one of Nup98's most important roles is knowing when to say, "Not yet."

"The protein's droplet-like condensates act as a temporary shield around damaged DNA, keeping out certain repair proteins that can cause trouble if they arrive too soon. One of those proteins, called Rad51, can accidentally stitch together the wrong pieces of DNA if it gets involved too early in the process.

"'The Nup98 droplets keep Rad51 away until other mechanisms have done their work to line up the correct pieces," Chiolo said. "Only once the damaged heterochromatin moves into a different nuclear space, Rad51 can safely finish the repair."

"By coordinating this carefully staged process, Nup98 helps cells avoid dangerous genetic rearrangements—a key part of maintaining genome stability and slowing processes responsible for cancer and aging."

Comment: having start and stop controls is a logical design. Which raises the evolutionary question did DNA appear with or without a repair mechanism? Surely not without. It seems simultaneous appearance of both is required. Only can happen by design.