A multidisciplinary team of Indiana University researchers have discovered that the motion of chromatin, the fabric that DNA is fabricated from, might help facilitate effective repair of DNA damage within the human nucleus — a finding that may lead to improved cancer diagnosis and treatment. Their findings were recently published within the Proceedings of the National Academy of Sciences.

DNA damage happens naturally in human body and many of the damage may be repaired by the cell itself. Nonetheless, unsuccessful repair may lead to cancer.

DNA within the nucleus is at all times moving, not static. The motion of its high-order complex, chromatin, has a direct role in influencing DNA repair. In yeast, past research shows that DNA damage promotes chromatin motion, and the high mobility of it also facilitates the DNA repair. Nonetheless, in human cells this relationship is more complicated.”

Jing Liu, assistant professor of physics, School of Science at IUPUI

Liu and his colleagues found that chromatin on the location of DNA damage moves much faster than those away from the DNA damage. In addition they found that the chromatin in cell nuclei shouldn’t be moving randomly. It is a coherent movement, with the DNA moving as a bunch over a brief distance.

The researchers also found evidence that DNA damage may affect the DNA’s group movement by reducing the coherence. These findings indicate that chromatin motion is under tight control when DNA is broken. This is significant to forestall the damaged DNA from harmful contact and to enhance the accuracy and efficacy of DNA repair, Liu said.

“Our findings reveal a fundamental role of the chromatin motion in DNA damage response and DNA repair,” Liu said. “These findings might help to grasp the mechanism of DNA repair in human cells and cancer initiation in humans. Practically, we will use these findings because the metrics for the drug response of many alternative drugs used to treat cancer. We will test different drugs to see if the chromatin motion may be modified to boost DNA repair.”

To be able to conduct this research, Liu and his colleagues needed to develop the computational tools obligatory for analyzing massive amounts of knowledge. With data sizes as large as a terabyte in some cases, Liu and his colleagues worked with IU’s University Information Technology Services to ascertain the Scalable Data Archive of highly dynamic cell images, which centralizes data storage, data transfer, and data processing.

In the long run, the researchers hope to check single DNA molecules and the way they’re moving, and the way individual and group dynamics differ and alter in response to DNA damage. They’d also prefer to learn more about DNA movement in specific genes which can be known to be more vulnerable to DNA damage.

Source:

Journal reference:

Locatelli, M., et al. (2022) DNA damage reduces heterogeneity and coherence of chromatin motions. PNAS. doi.org/10.1073/pnas.2205166119.