Weizmann scientists show DNA's shape decides whether damage gets repaired

A study led by Dr. Ariel Afek's laboratory at the Weizmann Institute of Science in Rehovot, Israel, with Prof. Brian P. Weiser and colleagues at Rowan University in New Jersey, has found that the physical shape of DNA around a damaged spot strongly influences whether the cell's repair machinery fixes it. The paper, with doctoral student Noga Levy as first author, appeared in Nature Communications in July 2026; the Weizmann Institute announced it on 10 August and it was widely reported later that month.

Every cell suffers constant chemical damage to its DNA. Specialised enzymes called glycosylases find and remove damaged letters, but when they miss a lesion it can become a permanent mutation, the raw material of cancer and other diseases. Scientists have long treated where such mutations occur as largely a matter of chance.

To test this, the team built DNA microchips carrying millions of sequences, each with the same type of damage in the same position but different surrounding letters. Fluorescent tags showed how readily repair enzymes bound to each version, and atomic-scale computer simulations at Rowan explained why. When neighbouring letters bend and narrow the DNA, a pocket of concentrated negative charge forms that draws the enzymes in. When the surrounding sequence keeps the DNA flatter, the damage is more likely to be left alone. Afek told The Times of Israel that bending or twisting could make repair about a hundred times easier or harder.

The researchers then compared their lab results with large human cancer databases, including The Cancer Genome Atlas. The sequence contexts that resisted repair on the chips matched known mutation hotspots in real tumours, suggesting the enzymes' structural preferences help predict where mutations pile up and may even have shaped the human genome over evolutionary time.

Afek cautioned that therapies are a long way off, but said the findings could eventually help scientists design customised repair enzymes or targeted treatments for cancer and neurodegenerative disorders.