Scientists Find System That Promotes DNA Repair and Genome Stability

Findings in a new study by researchers at the University of Toronto challenge a long-held belief that broken DNA moves about randomly within the nuclei of cells and eventually set off cellular changes.



In a paper published recently in Nature Communications, scientists revealed that they have found an intricate system that facilitates the repair of defective DNA. Broken genetic material does not always move around aimlessly, their findings show.

Evidence from the study challenges the deep-rooted belief that DNA breaks float aimlessly within cell nuclei. Such breaks, particularly double-strand breaks, constitute a considerable threat to cells.

Karim Mekhail, an associate professor of laboratory medicine and pathobiology at the University of Toronto, had observed that a system featuring filaments, liquid protein droplets, and protein connectors can make DNA repair possible.

Together with his colleagues, Mekhail found in 2015 that proteins can be used to move damaged DNA to areas with high amounts of repair factors – described as DNA “hospitals” – to enable repair.

Cells in the body depend on genome stability to function efficiently and promote overall health. DNA repair is crucial for this stability to be a reality.

This new research was multi-disciplinary, involving biologists, biochemists, and aerospace engineers. The lead author was Roxanne Oshidari, a postdoctoral fellow at U of T.

Exploring DNA repair

Researchers used yeast cells for this new study. The cells that were used had numerous double-strand DNA breaks.

Short microtubule filaments and liquid droplets featuring repair proteins work together to aid and support the process of DNA repair, the team found.

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“The liquid droplets work with intranuclear microtubules to promote the clustering of damaged DNA sites,” Mekhail stated. “Repair proteins at these different sites assemble in droplets that fuse into a larger repair-centre droplet, through the action of the shorter nuclear microtubules.”

The research team found that the bigger, oil-like droplet helps to ferry damaged DNA to “hospitals” for repair.

Computer simulations done in collaboration with Nasser Ashgriz, a professor of mechanical and industrial engineering at U of T, helped to shed more light on the repair process.



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