Researchers have discovered a new model for ‘global’ DNA repair


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The two studies provide a more up -to -date picture of how bacterial cells repair damaged parts (lesions) in their DNA.

Led by researchers from NYU Grossman School of Medicine, the work revolves around the taste of DNA molecules, which can be damaged by reactive products of cellular metabolism, toxins, and ultraviolet light. . Because damaged DNA can result in harmful DNA code changes (mutations) and death, cells have evolved that have DNA repair machines. A big question that hasn’t been resolved in school is how these machines can quickly search and find the few flaws among the “vast lands” of non -DNA.

Past studies have shown that a critical search engine – transcription -coupled repair or TCR – relies on RNA polymerase, the large (complex) protein complex that moves the DNA chain, reading code. the “letters” of DNA as it translates the instructions into RNA molecules, which then directs the construction of the protein. Current research is underway, however, and the TCR machine has been misdiagnosed, according to the research authors.

Of the most accepted works, including donations that led to a 2015 Noble Prize, TCR argued less work in editing because it relied on a putative TCR source that only provided a grant. marginal in DNA repair. A similar process, global genome repair (GGR), is thought to detect and repair most of the DNA independent of transcription. The two processes are intended to set the stage for nucleotide excision (NER) reconstruction, in which a specific piece of DNA is extracted and replaced by an accurate copy.

Two new studies will be published online March 30 in journals so so a Nature Communications agreement, by its first nature, multi-stage analysis of DNA regulatory survival E. coli cells, most, if not all, of which NER is combined with RNA polymerase, which checks the entire bacterial genetic code for damage.

“Based on our findings, we need to rethink some of the key concepts in DNA repair work,” said senior research author Evgeny Nudler, Ph.D., Julie Wilson Anderson Professor, Department of Biochemistry and Molecular Pharmacology, NYU Langone Health. “The real understanding of such treatment is that it is a major goal in medicine, even though most antibiotics and chemotherapies kill patients by damaging their DNA, and the it is possible to complete the treatment which will make it easier for existing drugs, ”Nudler said. is a fellow researcher with the Howard Hughes Medical Institute.

Information pipe

Past studies have not been able to fully capture the true nature of NER in bacteria, the current authors say, because they have used experiments that have tried to recreate the relationships. complex protein outside living cells. He led the school, for example, to describe a protein called Mfd as a protein player in TCR, even though most DNA repair is known to persist if present. Mfd or. Thus, TCR is considered a minor correction pathway. TCR is thought to be the only part of DNA that has been written extensively. Unwritten genomic areas, or parts of the genome that are considered “unwritten,” are considered “unwritten,” in the GGR.

The study was reprinted at so so He used a crosslinking mass spectrometry (XLMS) technology to record the distances between chemically bonded proteins, thus determining the contact surfaces of NERs. large and complex polymerases for the first time when they accumulate in living cells. The company provides spectrometry data in computer -driven simulations, eliminating real -world simulations.

Contrary to common dogma, the study of RNA polymerase is seen to serve as a scaffold for the synthesis of the entire NER complex, and as a precursor to DNA molecules. It was found that the major NER enzymes UvrA and UvrB do not detect most lesions on their own, but are provided by RNA polymerase. This TCR procedure is independent of Mfd, the authors said.

The second lesson, published in Nature Communications, new in living things, has used a high-throughput sequencing technology called CPD-seq to monitor the nature of DNA lesions by detection of UV light, and the speed of repair By deciphering a single nucleotide in the DNA code. . CPD-seq has been shown to inhibit bacterial transcription by using the antibiotic rifampicin to suppress regulation in the bacterial genome. Research suggests that NER is closely linked to transcription at all parts of the bacterial chromosome, the DNA system that stores all genes.

In a new interesting leap, experiments have shown that bacterial cells, in the presence of DNA damage, inhibit the action of the Rho protein, the cell -destroying signal that tells RNA polymerase to stop reading. By capturing the restorative signals, RNA polymerases are read, providing enzymes that repair DNA damage at all detected locations in the genome.

“To the best of our knowledge, we suggest that eukaryotes, as well as human cells, also use RNA polymerase for efficient regulation worldwide, even though the complex TCR bacteria described here are human analogues. , “said the first author of the so so to study with Binod Bharati, Ph.D., a post-doctoral specialist in Nudler’s lab. “Moving forward, our team plans to ensure the presence of global TCR in human systems, and if confirmed, to determine if safety management can be strengthened in the future. to fight the diseases of old age. ”

RNA molecules regulate human DNA repair in cancer cells

More information:
Evgeny Nudler, The critical role and nature of Transcription-coupled DNA Repair in Bacteria, so so (2022). DOI: 10.1038 / s41586-022-04530-6.

Presented by NYU Langone Health

Directions: Researchers found the latest model for ‘global’ DNA analysis (2022, March 30) retrieved on 30 March 2022 from html

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