Every living organism has DNA, and every living organism engages in DNA replication, the process by which DNA makes an exact copy of itself during cell division. While it’s a tried and tested process, problems can arise.
Break-through replication (A) is one way to solve these problems. In humans, it is mainly used to repair breaks in DNA that otherwise cannot be corrected. Yet BIR itself can lead to or cause genomic rearrangements and mutations that contribute to cancer development through repairs in DNA and how it performs those repairs.
“It’s a kind of double-edged sword,” says Anna Malkova, a professor at the University of Iowa Department of Biology, who has been working on BIR since 1995. “The basic ability to repair is a good thing, and there may be some DNA breaks that cannot be repaired by other means. So the idea is very good. But the results can be bad.”
A new study in the magazine under the leadership of Malkova Nature, He tries to explain BIR’s high-risk-reward arrangement by explaining for the first time his end-to-end sequence in A series. Biologists have developed a new technique in a yeast model that allows them to examine how BIR functions throughout the repair cycle. Until now, scientists had only been able to examine BIR’s operations at the beginning and end stages. The researchers then uncovered barriers to DNA replication, such as the process of copying DNA to produce proteins, believed to be helped by BIR.
“Our study shows that when BIR comes to rescue in these collisions, his arrival comes at a very high cost,” says Malkova, the study’s corresponding author. “When BIR encounters transcription, it can cause more imbalance, which can lead to higher mutations. As a result, we think that imbalances found in collisions between transcription and replication, which are alleged to lead to cancer, may be due to the BIR coming to the rescue. somewhat doubtful as useful. “
Scientists know how BIR works at some stages. For example, they know that the DNA repair apparatus creates a kind of bubble around the damaged DNA and then moves forward, unzips the DNA, duplicates intact parts, and will eventually transfer those copied parts to a new DNA strand.
But the tricky thing was to follow BIR through the entire repair cycle. Using a technique that included Droplet Digital PCR and a new DNA purification method developed by biology graduate student Liping Liu, the researchers were able to observe BIR from beginning to end.
“If you imagine it as a train, Liping set up a group of stations and watched how the train progressed at each station, watching the DNA increase at each station, how much increase was happening at each station, and therefore in the total, how the whole process evolved,” Malkova explains.
The team then deliberately introduced interceptions at some stations – another hurdle called transcription and internal telomere arrays – to observe how BIR responds to obstacles. One finding: When transcription is introduced at the beginning of the BIR process, repairs don’t start as if they were suppressed. In addition, the researchers found that the BIR-related orientation of transcription could affect the repair cycle and could be an important factor affecting the instability that could promote cancer in humans.
“Scientists already know that there is a lot of instability where high transcription meets normal reproduction,” Malkova says. “What we didn’t know until now is where it came from and why.”
Reference: Liu L, Yan Z, Osia BA, et al. The follow-up of the reproduction caused by the fracture shows that he stopped at the barricades. Nature. 2021. doi: 10.1038 / s41586-020-03172-w.
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