Chromatin Dynamics Facilitate DNA Repair

Chromatin is responsible for numerous cell processes, including DNA replication, transcription, repair, and more. When DNA is damaged, alterations also occur to the underlying chromatin structure and dynamics. The cell can often repair itself from minor damage, but this isn’t always the case in diseases such as cancer. Researchers from Indiana University decided to investigate chromatin’s role during DNA repair, and how these roles change based on their location.

The researchers, whose work was published in the Proceedings of the National Academy of Sciences, discovered that chromatin's motion is not random. It's a coherent effort of DNA moving in tandem. Additionally, they found that the chromatin located on the site of DNA damage moves much faster than chromatin located further away. 

"DNA in the nucleus is always moving, not static. The motion of its high-order complex, chromatin, has a direct role in influencing DNA repair," said Jing Liu, assistant professor of physics in the School of Science at IUPUI. "­In yeast, past research shows that DNA damage promotes chromatin motion, and the high mobility of it also facilitates the DNA repair. However, in human cells this relationship is more complicated."

While these findings are relatively focused on DNA damage, their approach has broad implications to applications in genome biology and cancer diagnostics. They began by visualizing defined patterns of chromatin microdomains, before overlaying the physical maps of chromatin dynamics with orthogonal readouts of DNA breaks and chromatin compaction within live cells. This approach sampled chromatin in different nuclear regions, revealing how DNA damaged their individual kinetics.

The team also found that chromatin motion is under tight restrictions when DNA is damaged and ultimately reduces coherence. "This is important to prevent the damaged DNA from harmful contact and to improve the accuracy and efficacy of DNA repair," says Liu. "These findings can help to understand the mechanism of DNA repair in human cells and cancer initiation in humans. Practically, we can use these findings as the metrics for the drug response of many different drugs used to treat cancer. We can test different drugs to see if the chromatin motion can be modified to enhance DNA repair."

For future work, the researchers hope to analyze single DNA molecules’ movements, both individually and in group dynamics, and how those movements alter in response to DNA damage. They also want to learn more about DNA movement within specific genes known to be extra vulnerable to DNA damage.