Everyone among the trillions of cell types in the human body experience greater than 10,000 DNA blemishes every day. These damages could be devastating if cells could not heal them. But the delicate mechanism that can detect and repair DNA damage is in place to stop DNA mutations from causing diseases like cancer.
Utilizing Machine Learning
Utilizing machine learning, applied to high-throughput microscopy, among other techniques. Research scientist Barbara Martinez, a member of the Metabolism and Cell Signalling Group directed by Alejo Efeyan from the National Cancer Research Centre (CNIO) and Raul Mostoslavsky, and the team of Massachusetts General Hospital (Boston, USA). They have been able to observe this DNA repair process in great detail. They also discovered novel repair protein molecules. The results, which were developed in Boston and developed between Boston and Madrid and released today by Cell Reports, could help develop new cancer treatments.
What Martinez Says About DNA Damages?
When there is DNA damage, like a DNA split, the cell triggers a DNA damage response. It functions as the “call to the emergency services,” Martinez says. Proteins quickly connect damaged DNA to signal alarms, which are recognized by other proteins that are specialized in the repair process.
The aim of chemotherapy is the kill cancer cells by causing DNA lesions. These can cause the cancer cells to collapse and eventually death.
DNA Machine-Learning Can Create Images Report?
Researchers have created an entirely new analysis method with the aid of a machine-learning analysis technique devised through the CNIO Confocal Unit. It has enabled the analysis of the process in a level of accuracy and clarity that was never before seen. “Until now, one limiting factor in tracking DNA repair kinetics was the inability to process. Moreover, analyze the amount of data generated from images taken by the microscope.”
What Role do Proteins Play in the Repairing of DNA?
Researchers have utilized high-throughput microscopes that allow the collection of hundreds of photos of cells following the induction by genetic injury. In the initial phase, they introduced over 300 proteins into cells and then assessed in one experiment whether they impeded the repair of DNA over time. This approach results from identifying nine proteins involved in the repair of DNA.
The authors, however, chose to go one step further and observe the 300 proteins following the occurrence of genetic damage. To achieve this, they altered an old DNA micro-irradiation method which causes DNA damage using the UV laser to use on a larger scale for the first time. They also studied the behavior of the 30 proteins they studied.
“We saw that many proteins adhered to damaged DNA, and others did just the opposite: they moved away from the DNA lesions. The fact that they either bind to or remove themselves from damaged DNA allows the recruitment of repair proteins to the lesion is a common feature of DNA repair proteins. Both phenomena are relevant”.
A protein identified is PHF20. The researchers found that this protein can move away from lesions in just a few seconds after damage, facilitating recruiting 53BP1, a key protein for DNA repair. Cells that lack PHF20 can’t repair their DNA correctly as well, and they are much more sensitive to radiation than normal cells, which suggests that PHF20 is essential in the repair of DNA.
These technologies present new possibilities to research DNA repair and alter it. “An advantage is that both platforms are very versatile and can be used to discover new genes or chemical compounds that affect DNA repair. We have evaluated hundreds of proteins in minimal time by using techniques allowing direct visualization of DNA repair.”
Journal reference: Martinez-Pastor, B., et al. (2021) Assessing kinetics and recruitment of DNA repair factors using high content screens. Cell Reports. doi.org/10.1016/j.celrep.2021.110176.