DNA 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. Now, researchers from the Kind Group at the Hubrecht Institute have 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. These findings may lead to new cancer therapies and other treatments where DNA repair is essential.
The researchers published their findings in Nature Communications in an article titled, “Genome-wide profiling of DNA repair proteins in single cells.”
“Accurate repair of DNA damage is critical for maintenance of genomic integrity and cellular viability,” the researchers wrote. “Because damage occurs non-uniformly across the genome, single-cell resolution is required for proper interrogation, but sensitive detection has remained challenging. Here, we present a comprehensive analysis of repair protein localization in single human cells using DamID and ChIC sequencing techniques.”
“Finding breaks in DNA is an enormous challenge,” explained first author Kim de Luca, PhD. “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 added. “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,” said de Luca. “A hub can involve as many as six different breaks that are being repaired in a coordinated way.”
