Replication is the greatest magic trick of nature. Pay close attention and you can see in front of your eyes how a single cell is blurred into two virtually identical copies. Presto.
After more than half a century of research in molecular genetics, it's easy to believe we've found this biological dab, but that's not the case.
Using the latest technologies, researchers have discovered crucial details that show how DNA determines its own replication.
"It was a mystery," says molecular biologist David Gilbert of Florida State University.
"Replication It seemed resilient to anything we tried to do to disturb it, as we have described in detail, showing that it changes in different cell types and that it is disturbed in disease.
"But until now, we could not find that piece, the controls, or the DNA sequences that control them. "
If you open any textbook on the subject, you'll find diagrams showing how long filaments of deoxyribonucleic acid (DNA) act like the world's longest puzzle and almost build identical strands through the use of clever chemistry and a host of industrialized ones Proteins.
Most of us have the luxury of glossing over the details of this enzymatic sorcery in light of the general tricks.
But for researchers, the sheer complexity of the process ̵
As with all good magic tricks, the timing is crucial, but the confusion with regulatory proteins does not seem to make as much difference as one might suspect, suggesting that the exact rhythm of replication tends to be on itself acting DNA molecule has to do.
To determine the chemical architecture In determining the timing of DNA replication, Gilbert and his team turned to the emerging technology known as CRISPR to isolate mouse chromosomes to find out what factors made a difference.
CRISPR is a molecular toolkit based on a process by which bacteria identify the genes of threatening viruses. When a specific genetic code is discovered, CRISPR-related enzymes can heal and break up the sequence, effectively eliminating the threat.
In the hands of researchers, the same system can be used to cut into a specific DNA sequence.
19659002] Gilbert used it to attack, switch, or eliminate completely different structures within the DNA architecture of mouse embryonic stem cells.
Initially, the focus was on the binding sites for a protein called CCCTC binding factor (CTCF). This protein contributes to the regulation of the entire transcription process, making its landing zone a natural site for locating DNA's temporal-temporal operations.
However, customizing these areas had little impact on the actual timing of replication processes. Something else had to be at work.
However, finding this virtual needle in a haystack required more than a little luck.
A high-resolution 3D analysis of the contact sites, which produced the DNA with itself. In a sense, like a close-up of an experienced wizard's hands at work, the team was able to find out which "fingertips" were in action.
In particular, they identified several key locations outside the boundaries associated with the CTFC. The breaking broke the chaos – the replication age was thrown, the DNA architecture itself was weakened and the transcription was overlooked.
"Removing these elements delayed the replication time of the segment from the beginning to the end of the process," says Gilbert.
"This was one of the moments when only one result shook off your socks."
Their findings open new avenues in health research and pathology. By finding the mechanisms responsible for the timing of DNA replication, researchers may uncover processes that lead to certain diseases.
"Duplicating elsewhere and at a different time allows you to build a completely different structure," says Gilbert. 19659002] We have come a long way since physicist Erwin Schrödinger made his prediction of an "aperiodic crystal" that could explain the replication of a cell by using little more than the physics of basic chemistry.
More than seven decades later The physics behind molecular genetics still does not share its secrets.
Not that the greatest magic of nature is less amazing.
This research was published in Cell .