DNA repair by cooperation between proteins: A look inside the cell's repair hub

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New research from the Kind Group at the Hubrecht Institute sheds light on how cells repair damaged DNA. For the first time, the team has mapped the activity of repair proteins in individual human cells.

The study demonstrates how these proteins collaborate in so-called "hubs" to repair DNA damage. This knowledge offers opportunities to improve cancer therapies and other treatments where DNA repair is essential. The researchers published their findings in Nature Communications on November 21.

DNA is the molecule that carries our genetic information. It can be damaged by normal cellular processes as well as external factors such as UV radiation and chemicals. Such damage can lead to breaks in the DNA strand. If DNA damage is not properly repaired, mutations can occur, which may result in diseases like cancer. Cells use repair systems to fix this damage, with specialized proteins locating and binding to the damaged regions.

The body has various mechanisms to repair DNA, but the process can differ from cell to cell. This makes it important to study DNA repair in individual cells.

"Finding breaks in DNA is an enormous challenge," explains first author Kim de Luca. "We don't know exactly where the damage occurs or why some areas are harder to repair. Our approach allowed us to answer these questions."

Using advanced techniques, the researchers mapped where repair proteins attach to DNA. "Previous studies looked at an average picture of multiple cells," De Luca explains. "By studying individual cells, we discovered unique and sometimes rare ways in which DNA damage is repaired."

The findings also revealed that DNA can be repaired by cooperation between repair proteins. These proteins organize themselves into "hubs," where multiple damaged DNA regions come together. These hubs are similar to "repair cafés," where people gather to fix broken items.

"Such a central place makes the process more efficient," says De Luca. "A hub can involve as many as six different breaks that are being repaired in a coordinated way."

The results of this study could contribute to better treatments for diseases involving DNA damage, such as cancer and genetic disorders. By understanding more about how cells repair DNA breaks, researchers can target specific DNA repair mechanisms.

"With precise knowledge of DNA repair, we can design new treatments that are both more effective and less harmful," says De Luca.

More information: Kim L. de Luca et al, Genome-wide profiling of DNA repair proteins in single cells, Nature Communications (2024). DOI: 10.1038/s41467-024-54159-4

Journal information: Nature Communications

Provided by Hubrecht Institute