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Repairing genetic breaks quickly and completely can be a matter of life and death for most organisms. Even the simplest changes in the sequence are likely to cause disaster, especially if the changed code is responsible for a critical function.
Over the past half-century, biologists have studied the mechanisms involved in the assembly of most of the key steps involved in making complete DNA repairs. However, part of the process has remained hopelessly unclear.
By labeling key enzymes and DNA with fluorescent markers and watching the repair process take place in real time in Escherichia coli Model, researchers at the University of Uppsala in Sweden filled in the missing details on how bacteria find the patterns they rely on to keep genetic repairs error-free.
One trick that most organisms use to keep their code in order is homologous recombination, the biological equivalent of comparing two different versions of a script to make sure the copy hasn’t accidentally introduced errors. .
By hanging an intact copy of the sequence next to the repair task, the cell can ensure that no changes will occur when the cut ends are glued together.
Molecular biologists have known for some time that the Rica protein recombinase plays a key role in managing this process. It is an important enzyme for maintaining the integrity of DNA, a transcription of which has been found in almost all of the species studied.
When the double-stranded DNA “ladder” is completely broken, a group of proteins work to pick up the cut ends and cut them precisely so that RecA can settle in and do its job.
Stretching into a long block, this protein comprises a strand of protein and DNA that is able to adhere to both the broken strand and an intact second strand of unbroken DNA.
Many scholars know this. From there, the wire should find the correct sequence to serve as a point of comparison. How the strands conduct this research in a fairly short time has been a mystery for nearly 50 years, multiplying across the millions of base pairs that must be examined amid complex chromosome twists.
To better understand the timing and navigation of the enzyme at work, researchers have developed thousands of coli bacteria The cells are found inside a series of tiny channels that allowed them to track individual bacteria during their experiments.
Once the cells were in place, the scientists made minute breaks in DNA using gene-editing CRISPRs, marking the cut ends with fluorescent markers to visualize the fracture site under a microscope.
“The microfluidic culture chip allows us to track the fate of thousands of individual bacteria simultaneously and monitor DNA disruption caused by CRISPR technology in a timely manner,” says Uppsala University molecular biologist Jacob Wiktor.
Finally, they used the antibodies to locate the RecA strands when they snap into place and start searching their library.
Report a chemical alert to the team when the entire repair process is complete. On average, it only took 15 minutes to coli bacteria to finish the job.
Surprisingly, it only took nine of those minutes for the protein to find the right pattern.
The secret seems to lie in the construction of the strands of the RecA nucleoprotein. This thread travels through the cell, grabs the chromosome, and slides down in search of a match with the sequence under its hand.
While this may seem ineffective, it’s really no different than methodically browsing the aisles of the library looking for a book that matches the catalog number.
“Since the ends of the DNA are embedded in these fibers, any part of the strands only need to find the valuable matrix, and so the search is theoretically reduced from three to two dimensions,” explains Arvid Gino.
“Our model suggests that this is the key to a quick and successful symmetry repair.”
Although this research was done on bacteria, the fact that RecA is similar throughout the biosphere makes it relevant to our bodies.
Now that we know how the process works, we can begin to look for signs of situations in which our DNA repair is going poorly, paving the way for understanding the origins of diseases like cancer.
This research was published in temper nature.
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