Without the ability to heal broken DNA, we would run the risk of developing cancer, as most oncogenes are associated with DNA repair.
How can a cell repair broken DNA? And how can the correct sequences of DNA be found to be used as a template in the crowded inside of the cell? These two questions have confused researchers for many years, and recently researchers from Uppsala University of Sweden provided answers.
A group of Swedish researchers led by Professor Johan Elf finally came up with a solution to the mystery, and presented their research results in a study published in the journal Nature in early September.
DNA recovery mechanisms
Over the past half century, biologists have studied the mechanisms involved in making DNA repairs, but an essential part of the process has remained unclear.
But by labeling key enzymes and DNA with fluorescent markers and monitoring the recovery process in real time in an E. coli model, the researchers bridged this knowledge gap about how bacteria find the templates on which they depend for genetic recovery.
When a DNA molecule splits into two parts, the fate of the cell is threatened, so repairing the rupture quickly is a matter of life or death for the cell, but repairing the DNA without making errors in the sequence importing is a big challenge as the repair machine has to find a template.
The process of repairing broken DNA using a template of a sister chromosome is known as “homologous recombination”, but the description usually ignores the tedious task of finding a matching template among all other genome sequences, because it is very clear that simple diffusion in 3D will not be fast enough.
The Rica molecule was involved in the research
Homologous recombination has been a mystery for at least 50 years, and previous studies have made it clear that the RecA molecule is involved in the search for a matching template within genome sequences, but this has been limiting our understanding of this process.
“Rica” is a protein responsible for DNA repair and maintenance, and its analogue in structural and functional structure has been found in all types of microorganisms, so that it has served as the ideal model for this class of proteins involved in DNA repair, and this ideal and identical model is present in all eukaryotic and prokaryotic organisms.
The Rica protein has several functions that are all related to DNA repair, for example in microorganisms such as bacteria it activates the self-catalyzed cleavage process of some inhibitors.
Use CRISPR technology
The researchers used a CRISPR-based technology to make controlled DNA breaks in bacteria. By culturing cells in a microfluidic culture slide and detecting RecA molecules with a fluorescence microscope, the researchers were able to reverse the process of homologous recombination of start to end image.
“The chip enables us to simultaneously track the fate of thousands of individual bacteria and to control CRISPR-induced DNA fragments in a timely manner,” said Jacob Wiktor, one of the researchers who conducted the study, in a press release from the Uppsala University said.
“It’s very precise, almost like having small DNA scissors,” he added.
Using microscopy, Professor Johann Elf and his team also found that the cell responds by rearranging the Reca molecule to form thin filaments that lengthen the length of the cell. They concluded that the entire recovery averaged 15 minutes completed, and that the form is completed within only about 9 minutes.
“We can see the formation of a thin, flexible structure coming out of the fracture site immediately after DNA damage,” said Arvid Gina, who worked on the project throughout his PhD, in the same press release.
What is the importance of this research?
The esteemed reader may ask: What is the importance of such research? The answer in short: it can help us understand the causes of tumor growth, because the process of symmetry recovery is almost identical for all organisms, including humans.
DNA damage occurs frequently in our bodies, and without the ability to heal broken DNA, we are more likely to develop cancer, as most oncogenes are associated with DNA repair, and new mechanistic insights can help us identify the causes. of tumor growth.
Recovering broken genes quickly and completely can be a matter of life or death for most organisms, as even the simplest changes in sequence can cause a catastrophe, especially if the altered code is responsible for a critical function.