DNA repair: A look inside the cell’s ‘repair café’

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.

Zooming in on individual cells

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.”

A ‘DNA repair café’

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.”

Toward more effective treatments

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.

About Job Kind

Jop Kind is group leader at the Hubrecht Institute, professor by special appointment of Single Cell Epigenomics at the Radboud University Nijmegen and Investigator at Oncode Institute. His group is interested in elucidating the role of chromatin and nuclear architecture in gene-regulation and DNA-repair. The Kind group develops new techniques, such as the recently developed DamID and ^m6ATracer techniques. These techniques enable them to study genome architecture and protein-DNA interactions in high resolution in single cells. The Kind group uses these techniques to study the role of genome architecture and chromatin context in temporal and spatial control of gene expression in development and disease.

About the Hubrecht Institute

The Hubrecht Institute is a research institute focused on developmental and stem cell biology. Because of the dynamic character of the research, the institute as a variable number of research group, around 20, that do fundamental, multidisciplinary research on healthy and diseased cells, tissues and organisms. The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), situated on Utrecht Science Park. Since 2008, the institute is affiliated with the UMC Utrecht, advancing the translation of research to the clinic. The Hubrecht Institute has a partnership with the European Molecular Biology Laboratory (EMBL). For more information, visit www.hubrecht.eu.