DNA in our body cells is damaged daily for a variety of reasons, so it can be said that intercellular DNA repair system is the basis for maintaining life, but for this basic mechanism scientists have not fully understand. Researchers from the University of North Carolina at Chapel Hill have used advanced sequencing techniques to clarify the key molecular details of these repair systems and have discovered the mystery of nucleotide excision repair.
The study was published in the February 6 issue of the journal PNAS. One of the authors of the paper was Prof. Aziz Sancar, one of the 2015 Nobel Laureates in Chemistry, who was born in Savoil, Turkey, and focused on DNA repair, Cycle checkpoints, biological clock aspects of the study. He was awarded the Nobel Prize for DNA repair research: he has spent a lot of time to analyze the mechanism of photolysis and photoactivation, these mechanisms have been exploring for nearly 20 years, direct observation of photolyase repair thymine dimer the process of.
To investigate excision repair in cells, Sancar et al. Developed a new technique: XR-seq, which allows researchers to isolate and sequencing small fragmented adducts that are cut from the genome during excision repair. Adduct-damaged) DNA. Understanding the sequence of these DNA fragments will help to more accurately locate their position in the genome.
Using this method, researchers in 2015 for the first time to build a human genome UV repair map, and in 2016 generated anti-cancer drug cisplatin on the entire human genome damage and repair map. Now they are using XR-seq technology to answer some of the basic problems of injury repair in E. coli, which will help the development of new antibiotic drugs.
In this study, the researchers found a protein: Mfd in bacterial excision repair plays a unique and important role.
"I think Mfd is the most interesting protein in E. coli," said Dr. Christopher P. Selby, one of the authors. Because when a bacterial gene is transcribed into RNA, the transcriptional machinery is stuck on a large adduct, where Mfd appears, recruiting additional repair proteins, and repairing the DNA damage. This process, led by Mfd, is called transcriptional coupling repair, which has a higher repair rate on the active transcribed DNA strands.
The researchers used the XR-seq method to analyze UV-induced damage in bacterial cells of E. coli and found clear evidence for transcriptional coupling repair in normal cells, but this repair was not possible in cells lacking Mfd, confirming Mfd The key role in this process.
In a further experiment, the researchers also found another excision repair protein: UvrD in Escherichia coli to help remove the damaged DNA excision fragments of the new role.
In the absence of UvrD, the excised DNA fragment will remain bound to the chromosomal DNA, making it difficult for the cell waste treatment enzyme to fragment and degrade. At the same time excision of the chain of repair proteins will be bound to the above, followed by excision of other sites of damaged DNA. The work of UvrD is to untangle these damaged and discarded DNA fragments from the chromosomal DNA so that they can be quickly processed into the next step, and the associated repair proteins can continue to undergo a new round of repair.
The next step is to use the XR-seq technique to resolve the detailed process of excision repair in bacterial cells, human and other mammalian cells.
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