AI Helping Blaze a New Trail in DNA Research

When a human cell divides, its DNA must be accurately replicated—this is essential to our health. If DNA replication contains errors, this can lead to severe disease. It is estimated that up to two-thirds of all cancers are caused by the buildup of errors in DNA replication.

Because of its importance to human health, DNA replication has become a heavily studied area in biomedical research. If we can better understand how cells accurately regulate DNA replication—and why they sometimes don’t—we can make great strides forward in disease prevention and treatment, improving well-being and saving lives.

Throughout 30 years of DNA research, a lingering puzzle regarding the behavior of an MCM protein complex and its role in DNA replication divided scientists around the world. Researchers remained perplexed by paradoxical facts relating to the MCM complex to the point that it became known as the “MCM paradox,” remaining unsolved until today.

Dr. Hana Polasek-Sedlackova, award-winning scientist, recently made several exciting discoveries in the field of DNA replication. One of these was the solving of the MCM paradox, made possible by Polasek-Sedlackova’s use of Evident’s scanR high-content screening station, a modular microscope-based imaging platform powered by TruAI™ deep-learning technology.
Previously, active MCMs had never been visualized at the site of DNA synthesis inside a cell, even though it was known that they played a major role in DNA replication, while an excess of inactive MCMs was visible (the “paradox”).

Using scanR high-content imaging and tagging and tracking MCMs, Polasek-Sedlackova and her team were able to successfully visualize MCM activity—and discovered that the excessive inactive MCMs act as natural replication pausing sites (NRPSs), hence minimizing errors during DNA replication.^1,2 The paradox was explained, and Polasek-Sedlackova discovered that NRPSs represent an attractive new target for cancer therapy.

“The scanR system played an important role in solving the MCM paradox,” Polasek-Sedlackova said. “I was particularly impressed by its ability to provide an unbiased and fully automated analysis of cellular processes. Given the current reproducibility crisis in scientific research, I firmly believe that researchers should pursue tools that enable them to obtain and analyze data in a fully automated manner, presenting an unbiased representation of cellular processes.”

While she appreciates many features of the scanR system, Polasek-Sedlackova said she is most impressed by its unique connection between automated acquisition and analysis, which enables her to perform multiparameter analysis of acquired images in real time.

“In the current era of AI, image analysis has advanced beyond its previous limitations,” she said. “The scanR system’s TruAI deep-learning module has greatly expanded the scope of my research. Previously, I focused primarily on analyzing single cells in large populations of cultured human cell lines. However, with TruAI, we can, for instance, conduct extremely precise image analysis of individual cells in organ sections.”

References

1. Polasek-Sedlackova H, Miller TCR, Krejci J, Rask MB, Lukas J. Solving the MCM paradox by visualizing the scaffold of CMG helicase at active replisomes. Nat Commun. 2022 Oct 14;13(1):6090. doi: 10.1038/s41467-022-33887-5. PMID: 36241664; PMCID: PMC9568601. https://www.nature.com/articles/s41467-022-33887-5

2. Sedlackova, H., Rask, M.-B., Gupta, R., Choudhary, C., Somyajit, K., Lukas, J. (2020, October 21). Equilibrium between nascent and parental MCM proteins protects replicating genomes. Nature News. https://www.nature.com/articles/s41586-020-2842-3