All organisms have DNA, and all living organisms are involved in DNA reproduction, the process by which DNA replicates itself during cell division. While it is a very trying process, problems can arise.
Reproductive stimulation (BIR) is a way to solve these problems. In humans, it is primarily employed to repair a break in DNA that cannot be repaired. But BIR itself, through its repair of DNA and how it does that repair, can introduce genetics and mutations that contribute to the development of cancer.
“It’s kind of a two-edged sword,” says Anna Malkova, a professor in the Department of Biology at the University of Iowa, who has studied BIR since 1995. “It’s a good thing basic ability to repair, and some DNA fragmentation can be repaired by other means. So the idea is very good. But the consequences can be bad. “
A new study led by Malkova, published Jan. 20 in the magazine Nature, attempting to find a high-risk BIR reward solution by reporting for the first time on the start-to-finish sequence in BIR. The biologists developed a new method that allowed them to study in a yeast model how BIR works during its repair cycle. Until now, scientists have not been able to study the activity of BIR at the beginning and end stages. The researchers then introduced barriers to DNA reproduction, such as transcription – the process of DNA copying to produce proteins – which is believed to be supported by BIR.
“Our study shows that when BIR comes to the rescue at these accidents, it comes at a very high price,” says Malkova, co-author of the study. “When BIR encounters a transcript, it can introduce even more instability, which could lead to even higher mutations. As a result, we believe that instability could has been found mainly at accidents between transcription and reproduction that have been suggested to cause cancer.with BIR who came to the rescue.He will come, he will save, but it is somewhat doubtful what how helpful it really is. “
Scientists know how BIR works at certain levels. For example, they know that the DNA repair mechanism creates bubbles of sorts around the damaged DNA, then moves forward, extracting the DNA, making semi- plaques of whole sections, and finally move those copy pieces to new DNA strands.
But what was left was hard to follow BIR throughout its repair cycle. Using a method of Droplet Digital PCR and a new DNA cleansing technique developed by biology graduate student Liping Liu, the researchers were able to observe BIR from start to finish.
“If you think of this as a train, Liping installed a base of stations, and she looked at how the train went at each station, monitoring the increase in DNA at each station, what the increase is. occurs at every station, and therefore, as a whole. , as the whole process expands, “Malkova explains.
The team then introduced barriers at some stations – transcription and other obstruction called inner telomere sequences – to see how BIR dealt with the obstacles. One finding: when a rewrite is introduced near the beginning of the BIR process, the repair work will not begin, as if they had been delivered. Also, the researchers found that the transcriptional guidance regarding BIR can affect the repair cycle and this may be an important factor influencing cancer-induced instability in humans.
“Scientists already know that there is a lot of instability in places where high transcription meets normal reproduction,” Malkova says. “What we didn’t know so far is where it comes from and why it’s happening.”
The first author of the study, “Monitoring a frustrated replica that stops at roadblocks,” is Liu, a sixth-year graduate student at Malkova’s lab. Co-authors from Iowa include Beth Osia, Jerzy Twarowski, Juraj Kramara, Rosemary Lee, Hanzeng Li, and Rajula Elango (now at Beth Israel Deaconess Medical Center and Harvard Medical School). Co-authors from Baylor College of Medicine include Zhenxin Yan, Luyang Sun, Sandeep Kumar, Weiwei Dang, and Grzegorz Ira.